Abstract
The knowledge of the mechanisms regulating electric neuronal activity is fragmented by the wide variety of techniques and experimental models currently used in neurophysiological research. The interest and importance of the results obtained in any research is improved when interpreted in the perspective of the organism functioning as a whole in physiological conditions. Such interpretation, freed of the constraints imposed by the different techniques and experimental conditions used, is especially important when discussing together results obtained at the behavioral, cellular, and molecular level. This article outlines some of the key factors to consider when experiments from different models are interpreted together.
Similar content being viewed by others
References
Bernard C. (1865) L'Introduction à l'étude de la médecine expérimentale. Garnier-Flammarion, Paris.
Bremer F. (1958) Cerebral and cerebellar potentials. Physiol. Rev. 38, 357–388.
Creutzfeldt O. D., Watanabe S., and Lux H. D. (1966) Relations between EEG phenomena and potentials of single cortical cells. I. Evoked responses after thalamic and erpicortical stimulation. Electroencephalogr. Clin. Neurophysiol. 20, 1–18.
Creutzfeldt O. D., Watanabe S., and Lux H. D. (1966) Relations between EEG phenomena and potentials of single cortical cells. II. Spontaneous and convulsoid activity. Electroencephalogr. Clin. Neurophysiol. 20, 19–37.
Eccles J. C. (1951) Interpretation of action potentials evoked in the cerebral cortex. Electroencephalogi. Clin. Neurophysiol. 3, 449–464.
Hamill O. P., Marty A., Neher E., Sakmann B., and Sigworth F. J. (1981) Improved patchclamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 391, 85–100.
Windels F. and Kiyatkin E. A. (2004) GABA, not glutamate, controls the activity of substantia nigra reticulata neurons in awake, unrestrained rats. J Neurosci 24, 6751–6754.
Steriade M. (2001) Impact of network activities on neuronal properties in corticothalamic systems. J. Neurophysiol. 86, 1–39.
Volgushev M., Kudryashov I., Chistiakova M., Mukovski M., Niesmann J., and Eysel U. T. (2004) Probability of transmitter release at neocortical synapses at different temperatures. J. Neurophysiol. 92, 212–220.
Volgushev M., Vidyasagar T. R., Chistiakova M., and Eysel U. T. (2000) Synaptic transmission in the neocortex during reversible cooling. Neuroscience 98, 9–22.
Volgushev M., Vidyasagar T. R., Chistiakova M., Yousef T., and Eysel U. T. (2000) Membrane properties and spike generation in rat visual cortical cells during reversible cooling. J. Physiol. 522(Pt 1), 59–76.
Kirov S. A., Sorra K. E., and Harris K. M. (1999) Slices have more synapses than perfusion-fixed hippocampus from both young and mature rats. J. Neurosci. 19, 2876–2886.
Miller J. D., Farber J., Gatz P., Roffwarg H., and German D. C. (1983) Activity of mesencephalic dopamine and non-dopamine neurons across stages of sleep and walking in the rat. Brain Res. 273, 133–141.
Souliere F, Urbain N, Gervasoni D., et al. (2000) Single-unit and polygraphic recordings associated with systemic or local pharmacology: a multi-purpose stereotaxic approach for the awake, anaesthetic-free, and head-restrained rat. J. Neurosci. Res. 61, 88–100.
Borbely A. A. (1978) Effects of light on sleep and activity rhythms. Prog. Neurobiol. 10, 1–31.
Klein D., Moore R. Y., and Reppert S. M. (1991) Suprachiasmatic nucleus. In: The Mind's Clock, Oxford University Press, New York, p. 467.
Wagner S., Sagiv N., and Yarom Y. (2001) GABA-induced current and circadian regulation of chloride in neurones of the rat suprachiasmatic nucleus. J. Physiol. 537, 853–869.
Abe M, Herzog E. D., Yamazaki S., et al. (2002) Circadian rhythm in isolated brain regions. J. Neurosci. 22, 350–356.
Tononi G., Cirelli C., and Pompeiano M. (1995) Changes in gene expression during the sleepwaking cycle: a new view of activating systems. Arch. Ital. Biol. 134, 21–37.
Martinez-Vargas M., Murillo-Rodriguez E., Gonzalez-Rivera R., et al. (2003) Sleep modulates cannabinoid receptor 1 expression in the pons of rats. Neuroscience 117, 197–201.
Dolci C., Montaruli A., Roveda E., et al. (2003) Circadian variations in expression of the trkB receptor in adult rat hippocampus. Brain Res. 994, 67–72.
Por S. B. and Bondy S. C. (1981) Regional circadian variation of acetylcholine muscarinic receptors in the rat brain. J. Neurosci. Res. 6, 315–318.
Castaneda T. R., de Prado B. M., Prieto D., and Mora F. (2004) Circadian rhythms of dopamine, glutamate and GABA in the striatum and nucleus accumbens of the awake rat: modulation by light. J. Pineal. Res. 36, 177–185.
Esquifino A. I., Cano P., Chacon F., Reyes Toso C. F., and Cardinali D. P. (2002) Effect of aging on 24-hour changes in dopamine and serotonin turnover and amino acid and somatostatin contents of rat corpus striatum. Neurosignals 11, 336–344.
de Saint Hilaire Z., Orosco M., Rouch C., Python A., and Nicolaidis S. (2000) Neuromodulation of the prefrontal cortex during sleep: a microdialysis study in rats. Neuroreport 11, 1619–1624.
Burlet S. and Cespuglio R. (1997) Voltammetric detection of nitric oxide (NO) in the rat brain: its variations throughout the sleepwake cycle. Neurosci. Lett. 226, 131–135.
Mochizuki T., Yamatodani A., Okakura K., Horii A., Inagaki N., and Wada H., (1992) Circadian rhythm of histamine release from the hypothalamus of freely moving rats. Physiol. Behav. 51, 391–394.
Nitz D. and Siegel J. M. (1996) GABA release in posterior hypothalamus across sleep-wake cycle. Am. J. Physiol. 271, R1707-R1712.
Aston-Jones G. and Bloom F. E. (1981) Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J. Neurosci. 1, 876–886.
Foot S. L., Aston-Jones G., and Bloom F. E. (1980) Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal. Proc. Natl. Acad. Sci. USA 77, 3033–3037.
Datta S. and Siwek D. F. (2002) Single cell activity patterns of pedunculopontine tegmentum neurons across the sleep-wake cycle in the freely moving rats. J. Neurosci. Res. 70, 611–621.
Gervasoni D., Darracq L., For P., Souliere F., Chouvet G., and Luppi P. H. (1998) Electrophysiological evidence that noradrenergic neurons of the rat locus coeruleus are tonically inhibited by GABA during sleep. Eur. J. Neurosci. 10, 964–970.
Gervasoni D., Peyron C., Rampon C., et al. (2000) Role and origin of the GABA ergic innervation of dorsal raphe serotonergic neurons. J. Neurosci. 20, 4217–4225.
Lee M. G., Manns I. D., Alonso A., and Jones B. E. (2004) Sleep-wake related discharge properties of basal forebrain neurons recorded with micropipettes in head-fixed rats. J. Neurophysiol. 92, 1182–1198.
Urbain N., Gervasoni D., Souliere F., et al. (2000) Unrelated course of subthalamic nueleus and globus pallidus neuronal activities across vigilance states in the rat. Eur. J. Neurosci. 12, 3361–3374.
Markus R. P., Santos J. M., Zago W., and Reno L. A. (2003) Melatonin nocturnal surge modulates nicotinic receptors and nicotine-induced [3H]glutamate release in rat cerebellum slices. J. Pharmacol. Exp. Ther. 305, 525–530.
Prospero-Garcia O., Miller D. R., and Henriksen S. J. (1993) Hippocampal interneuron activity in unanesthetized rats: relationship to the sleep-wake cycle. Neurosci. Lett. 156, 158–162.
Mason R. (1986) Chcadian variation in sensitivity of suprachiasmatic and lateral geniculate neurones to 5-hydroxytryptamine in the rat. J Physiol 377, 1–13.
Cain S. W., Verwey M., Hood S., et al. (2004) Reward and aversive stimuli produce similar nonphotic phase shifts. Behav. Neurosci. 118, 131–137.
van Gool W. A. and Mirmiran M. (1983) Agerelated changes in the sleep pattern of male adult rats. Brain Res. 279, 394–398.
van Gool W. A. and Mirmiran M. (1986) Effects of aging and housing in an enriched environment on sleep-wake patterns in rats. Sleep 9, 335–347.
van Gool W. A., Witting W., and Mirmiran M. (1987) Age-related changes in circadian sleep-wakefulness rhythms in male rats isolated from time cues. Brain Res. 413, 384–387.
Mendelson W. B. and Bergmann B. M. (1999) Age-related changes in sleep in the rat. Sleep 22, 145–150.
Clement P., Gharib A., Cespuglio R., and Sarda N. (2003) Changes in the sleep-wake cycle architecture and cortical nitric oxide release during ageing in the rat. Neuroscience 116, 863–870.
Mitsushima D., Mizuno T., and Kimura F. (1996) Age-related changes in diurnal acetylcholine release in the prefrontal cortex of male rats as measured by microdialysis. Neuroscience 72, 429–434.
Apartis E., Poindessous-Jazat F, Epelbaum J, and Bassant M. H. (2000) Age-related changes in rhythmically bursting activity in the medial septum of rats. Brain Res. 876, 37–47.
Bassant M. H. and Poindessous-Jazat F. (2002) Sleep-related increase in activity of mesopontine neurons in old rats. Neurobiol. Aging 23, 615–624.
Scheving L. E., Harrison W. H., Gordon P., and Pauly J. E. (1968) Daily fluctuation (circadian and ultradian) in biogenic amines of the rat brain. Am. J. Physiol. 214, 166–173.
Dietl H., Prast H., and Philippu A. (1993) Pulsatile release of catecholamines in the hypothalamus of conscious rats. Naunyn Schmiedebergs Arch. Pharmacol. 347, 28–33.
Simon M. L. and George R. (1975) Diurnal variations in plasma corticosterone and growth hormone as correlated with regional variations in norepinephrine dopamine and serotonin content of rat brain. Neuroendocrinology 17, 125–138.
Eriksson E., Eden, Modigh K., and Haggendal J. (1980) Ultradian rhythm in rat hypothalamic dopamine levels. J. Neural. Transm. 48, 305–310.
Kafka M. S., Wirz-Justice A., and Naber D. (1981) Circadian and seasonal rhythms in alpha- and beta-adrenergic receptors in the rat brain. Brain Res. 207, 409–419.
Naber D., Wirz-Justice A., Kafka M. S., and Wehr T. A. (1980) Dopamine receptor binding in rat striatum: ultradian rhythm and its modification by chronic imipramine. Psychopharmacology (Berl.) 68, 1–5.
Prast H., Grass K., and Philippu A. (1997) The ultradian EEG rhythm coincides temporally with the ultradian rhythm of histamine release in the posterior hypothalamus. Naunyn. Schmiedebergs Arch. Pharmacol. 356, 526–528.
van Dijk G. and Strubbe J. H. (2003) Timedependent effects of neuropeptide Y infusion in the paraventricular hypothalamus on ingestive and associated behaviors in rats. Physiol. Behav. 79, 575–580.
Grass K., Prast H., and Philippu A. (1995) Ultradian rhythm in the delta and theta frequency bands of the EEG in the posterior hypothalamus of the rat. Neurosci. Lett. 191, 161–164.
Naber D., Wirz-Justice A., Kafka M. S., Tobler I., and Borbely, A. A. (1981) Seasonal variations in the endogenous rhythm of dopamine receptor binding in rat striatum. Biol. Psychiatry 16, 831–835.
Barnes C. A. (1994) Normal aging: regionally specific changes in hippocampal synaptic transmission. Trends Neurosci. 17, 13–18.
Rosenzweig E. S. and Barnes C. A. (2003) Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog. Neurobiol. 69, 143–179.
Nakamura H., Kobayashi S., Ohashi Y., and Ando S. (1999) Age-changes of brain synapses and synaptic plasticity in response to an enriched environment. J. Neurosci. Res. 56, 307–315.
Bertoni-Freddari C., Giuli C., Pieri C., and Paci D. (1986) Age-related morphological rearrangements of synaptic junctions in the rat cerebellum and hippocampus. Arch. Gerontol. Geriatr. 5, 297–304.
Foster T. C., Barnes C. A., Rao G., and McNaughton B. L. (1991) Increase in perforant path quantal size in aged F-344 rats. Neurobiol. Aging 12, 441–448.
Consolo S., Wang J. X., Fiorentini F., Vezzani A., and Ladinsky H. (1986) In vivo and in vitro studies on the regulation of cholinergic neurotransmission in striatum, hippocampus and cortex of aged rats. Brain Res. 374, 212–218.
Jasek M. C. and Griffith W. H. (1998) Pharmacological characterization of ionotropic excitatory amino acid receptors in young and aged rat basal forebrain. Neuroscience 82, 1179–1194.
Wenk G. L. and Barnes C. A. (2000) Regional changes in the hippocampal density of AMPA and NMDA receptors across the lifespan of the rat. Brain Res. 885, 1–5.
Wenk G. L., Walker L. C., Price D. L., and Cork L. C. (1991) Loss of NMDA, but not GABA-A, binding in the brains of aged rats and monkeys. Neurobiol. Aging 12, 93–98.
Pagliusi S. R., Gerrard P., Abdallah M., Talabot D., and Catsicas S. (1994) Age-related changes in expression of AMPA-selective glutamate receptor subunits: is calcium-permeability altered in hippocampal neurons? Neuroscience 61, 429–433.
Cepeda C., Li Z., and Levine M. S. (1996) Aging reduces neostriatal responsiveness to N-methyl-D-aspartate and dopamine: an in vitro electrophysiological study. Neuroscience 73, 733–750.
Gonzales R. A., Brown L. M., Jones T. W., Trent R. D., Westbrook S. L., and Leslie S. W. (1991) N-methyl-D-aspartate mediated responses decrease with age in Fischer 344 rat brain. Neurobiol. Aging 12, 219–225.
Segal M. (1982) Changes in neurotransmitter actions in the aged rat hippocampus. Neurobiol. Aging 3, 121–124.
Griffith W. H. and Murchison D. A. (1995) Enhancement of GABA-activated membrane currents in aged Fischer 344 rat basal forebrain neurons. J. Neurosci. 15, 2407–2416.
Godefroy F., Bassant M. H., Lamour, Y., and Weil-Fugazza J. (1991) Effect of aging on dopamine metabolism in the rat cerebral cortex: a regional analysis. J. Neural. Transm. Gen. Sect. 83, 13–24.
Godefroy F., Bassant M. H., Weil-Fugazza J., and Lamour Y. (1989) Age-related changes in dopaminergic and serotonergic indices in the rat forebrain. Neurobiol. Aging 10, 187–190.
Ou X., Buckwalter G., McNeill T. H., and Walsh J. P. (1997) Age-related change in shortterm synaptic plasticity intrinsic to excitatory striatal synapses. Synapse 27, 57–68.
Foster T. C., Sharrow K. M., Masse J. R., Norris C. M., and Kumar A. (2001) Calcineurin links Ca2+ dysregulation with brain aging. J. Neurosci. 21, 4066–4073.
Norris C. M., Halpain S., and Foster T. C. (1998) Reversal of age-related alterations in synaptic plasticity by blockade of L-type Ca2+ channels. J. Neurosci. 18, 3171–3179.
Fernandez-Teruel A., Gimenez-Llort L., Escorihuela R. M., et al. (2002) Early-life handling stimulation and environmental enrichment: are some of their effects mediated by similar neural mechanisms? Pharmacol. Biochem. Behav. 73, 233–245.
Green E. J., Greenough W. T., and Schlumpf B. E. (1983) Effects of complex or isolated environments on cortical dendrites of middle-aged rats. Brain Res. 264, 233–240.
Moser E. I., Moser M. B., and Andersen P. (1994) Potentiation of dentate synapses initiated by exploratory learning in rats: dissociation from brain temperature, motor activity, and arousal. Learn. Mem. 1, 55–73.
Moser M. B., Trommald M., and Andersen P. (1994) An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses. Proc. Natl. Acad. Sci. USA 91, 12,673–12,675.
Moser M. B., Trommald M., Egeland T., and Andersen P. (1997) Spatial training in a complex environment and isolation alter the spine distribution differently in rat CA1 pyramidal cells. J. Comp. Neurol. 380, 373–381.
Gagne J., Gelinas S., and Martinoli M. G., et al (1998) AMPA receptor properties in adult rat hippocampus following environmental enrichment. Brain Res. 799, 16–25.
Rasmuson S., Olsson T., and Henriksson B. G., et al. (1998) Environmental enrichment selectively increases 5-HT1A receptor mRNA expression and binding in the rat hippocampus. Brain Res Mol Brain Res 53, 285–290.
Green E. J. and Greenough W. T. (1986) Altered synaptic transmission in dentate gyrus of rats reared in complex environments: evidence from hippocampal slices maintained in vitro. J. Neurophysiol. 55, 739–750.
Beaulieu C. and Cynader M. (1990) Effect of the richness of the environment on neurons in cat visual cortex. II. Spatial and temporal frequency characteristics. Brain Res. Dev. Brain Res. 53, 82–88.
Beaulieu C. and Cynader M. (1990) Effect of the richness of the environment on neurons in cat visual cortex. I. Receptive field properties. Brain Res. Dev. Brain Res. 53, 71–81.
Davis C. D., Jones F. L., and Derrick B. E. (2004) Novel environments enhance the induction and maintenance of long-term potentiation in the dentate gyrus. J. Neurosci. 24, 6497–6506.
Coq J. O. and Xerri C. (1998) Environmental enrichment alters organizational features of the forepaw representation in the primary somatosensory cortex of adult rats. Exp. Brain Res. 121, 191–204.
Doherty M. D. and Gratton A. (1992) High-speed chronoamperometric measurements of mesolimbic and nigrostriatal dopamine release associated with repeated daily stress. Brain Res. 586, 295–302.
Singewald N., Kaehler S., Hemeida R., and Philippu A. (1997) Release of serotonin in the rat locus coeruleus: effects of cardiovascular, stressful and noxious stimuli. Eur. J. Neurosci. 9, 556–562.
Singewald N., Kaehler S. T., and Philippu A. (1999) Noradrenaline release in the locus coeruleus of conscious rats is triggered by drugs, stress and blood pressure changes. Neuroreport 10, 1583–1587.
Zaichenko M. I., Mikhailova N. G., and Raigorodskii Yu. V. (2001) Neuron activity in the prefrontal cortex of the brain in rats with different typological characteristics in conditions of emotional stimulation. Neurosci. Behav. Physiol. 31, 299–304.
Ohta H., Honma S., Abe H., and Honma K. (2003) Periodic absence of nursing mothers phase-shifts circadian rhythms of clock genes in the suprachiasmatic nucleus of rat pups. Eur. J. Neurosci. 17, 1628–1634.
Mattson M. P. (2000) Neuroprotective signaling and the aging brain: take away my food and let me run. Brain Res. 886, 47–53.
Mattson M. P., Duan W., Lee, J., and Guo Z. (2001) Suppression of brain aging and neurodegenerative disorders by dietary restriction and environmental enrichment: molecular mechanisms. Mech. Ageing Dev. 122, 757–778.
Duan W., Lee J., Guo Z., and Mattson M. P. (2001) Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury. J. Mol. Neurosci. 16, 1–12.
Thibault L. (1992) Influence of feeding paradigm in rats on temporal pattern of: II. Brain serotoninergic and catecholaminergic systems. Chronobiol. Int. 9, 19–34.
Hamilton M. E. and Freeman A. S. (2004) Diet and chronic haloperidol effects on rat midbrain dopamine neurons. Synapse 53, 1–5.
Bianki V. L. (1981) Individual and species interhemispheric asymmetry in animals. Neurosci. Behav. Physiol. 11, 27–34.
Perez H., Ruiz S., Hernandez A., and Soto-Moyano R. (1990) Asymmetry of interhemispheric responses evoked in the prefrontal cortex of the rat. J. Neurosci. Res. 25, 139–142.
Schaap J., Albus H., Eilers P. H., Detari L., and Meijer J. H. (2001) Phase differences in electrical discharge rhythms between neuronal populations of the left and right suprachiasmatic nuclei. Neuroscience 108, 359–363.
Scharfman H. E., Sollas A. L., Smith K. L., Jackson M. B., and Goodman J. H. (2002) Structural and functional asymmetry in the normal and epileptic rat dentate gyrus. J. Comp. Neurol. 454, 424–439.
Walker Q. D., Rooney M. B., Wightman R. M., and Kuhn C. M. (2000) Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry. Neuroscience 95, 1061–1070.
Pogun S., Demirgoren S., Kutay F. Z., and Okur B. (1992) Learning induces changes in the central cholinergic system of the rat in a sexually dimorphic pattern. Int. J. Psychophysiol. 13, 17–23.
Pogun S., Kanit L., and Okur B. E. (1992) Learning-induced changes in D2 receptors of rat brain are sexually dimorphic. Pharmacol. Biochem. Behav. 43, 71–75.
Nabeshima T., Yamaguchi K., Yamada K., et al. (1984) Sex-dependent differences in the pharmacological actions and pharmacokinetics of phencyclidine in rats. Eur. J. Pharmacol. 97, 217–227.
Meyer H. (1899) Zur theorie der alkoholnarkose. Arch. Exp. Pathol. Pharmakol. 42, 109–118.
Overton E. (1991) Studien uber die narkose, zugleich ein Beitrag zur allgemeinen pharmakologie. Gustav Fischer, Jena, Germany. Trad. Ed. R. L. Lipnick. Chapmann and Hall, New York.
Franks N. P. and Lieb W. R. (1978) Where do general anaesthetic act? Nature 274, 339–342.
Franks N. P. and Lieb W. R. (1990) Mechanisms of general anesthesia. Environ. Health Perspect. 87, 199–205.
Franks N. P. and Lieb W. R. (1988) Volatile general anaesthetics activate a novel neuronal K+ current. Nature 333, 662–664.
Gruss M., Bushell T. J., Bright D. P., Lieb W. R., Mathie A., and Franks N. P. (2004) Two-poredomain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol. Pharmacol. 65, 443–452.
Patel A. J. and Honore E. (2001) Anesthetic-sensitive 2P domain K+ channels, Anesthesiology 95, 1013–1021.
Shin W. J. and Winegar B. D. (2003) Modulation of noninactivating K+ channels in rat cerebellar granule neurons by halothane, isoflurane, and sevoflurane. Anesth. Analg. 96, 1340–1344, table of contents.
Patel A. J., Honore E., Lesage F., Fink M., Romey G., and Lazdunski M. (1999) Inhalational anesthetics activate two-pore-domain background K+ channels. Nat. Neurosci. 2, 422–426.
Patel A. J. and Honore E. (2001) Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci. 24, 339–346.
Yost C. S. (2003) Update on tandem pore (2P) domain K+ channels. Curr. Drug Targets 4, 347–351.
Talley E. M., Sirois J. E., Lei Q., and Bayliss D. A. (2003) Two-pore-Domain (KCNK) potassium channels: dynamic roles in neuronal function. Neuroscientist 9, 46–56.
Maingret F., Patel A. J., Lazdunski M., and Honore E. (2001) The endocannabinoid anandamide is a direct and selective blocker of the background K(+) channel TASK-1. EMBO J. 20, 47–54.
Sirois J. E., Lynch C. 3rd, and Bayliss D. A. (2002) Convergent and reciprocal modulation of a leak K+ current and I(h) by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones. J. Physiol. 541, 717–729.
Takenoshita M. and Steinbach J. H. (1991) Halothane blocks low-voltage-activated calcium current in rat sensory neurons. J. Neurosci. 11, 1404–1412.
Bleakman D., Jones M. V., and Harrison N. L. (1995) The effects of four general anesthetics on intracellular [Ca2+] in cultured rat hippocampal neurons. Neuropharmacology 34, 541–551.
Ries C. R. and Puil E. (1993) Isoflurane prevents transitions to tonic and burst firing modes in thalamic neurons. Neurosci. Lett. 159, 91–94.
Llinas R., Sugimori M., Hillman D. E., and Cherksey B. (1992) Distribution and functional significance of the P-type, voltage-dependent Ca2+ channels in the mammalian central nervous system. Trends Neurosci. 15, 351–355.
Hall A. C., Lieb W. R., and Franks N. P. (1994) Insensitivity of P-type calcium channels to inhalational and intravenous general anesthetics. Anesthesiology 81, 117–123.
Friederich P., Benzenberg D., and Urban, B. W. (2001) Ketamine and propofol differentially inhibit human neuronal K(+) channels. Eur. J. Anaesthesiol. 18, 177–183.
Berg-Johnsen J. and Langmoen I. A. (1990) Mechanisms concerned in the direct effect of isoflurane on rat hippocampal and human neocortical neurons. Brain Res. 507, 28–34.
Fujiwara N., Higashi H., Nishi S., Shimoji K., Sugita S., and Yoshimura M. (1988) Changes in spontaneous firing patterns of rat hippocampal neurones induced by volatile anaesthetics. J. Physiol. 402, 155–175.
Berg-Johnsen J. and Langmoen I. A. (1986) The effect of isoflurane on unmyelinated and myelinated fibres in the rat brain. Acta. Physiol. Scand. 127, 87–93.
Mikulec A. A., Pittson S., Amagasu S. M., Monroe F. A., and MacIver M. B. (1998) Halothane depresses action potential conduction in hippocampal axons. Brain Res. 796, 231–238.
Franks N. P. and Lieb W. R. (1993) Selective actions of volatile general anaesthetics at molecular and cellular levels. Br. J. Anaesth. 71, 65–76.
Dilger J. P. (2002) The effects of general anaesthetics on ligand-gated ion channels. Br. J. Anaesth. 89, 41–51.
Yamakura T., Bertaccini E., Trudell J. R., and Harris R. A. (2001) Anesthetics and ion channels: molecular models and sites of action. Annu. Rev. Pharmacol. Toxicol. 41, 23–51.
Lingamaneni R. and Hemmings H. C. Jr. (2003) Differential interaction of anaesthetics and antiepileptic drugs with neuronal Na+ channels, Ca2+ channels, and GABA(A) receptors. Br. J. Anaesth. 90, 199–211.
Tanelian D. L., Kosek P., Mody I., and MacIver M. B. (1993) The role of the GABAA receptor/chloride channel complex in anesthesia. Anesthesiology 78, 757–776.
Yamakura T., Borghese C., and Harris R. A. (2000) A transmembrane site determines sensitivity of neuronal nicotinic acetylcholine receptors to general anesthetics. J. Biol. Chem. 275, 40,879–40,886.
Nishikawa K. and MacIver M. B. (2000) Membrane and synaptic actions of halothane on rat hippocampal pyramidal neurons and inhibitory interneurons. J. Neurosci. 20, 5915–5923.
Zimmerman S. A., Jones M. V., and Harrison N. L. (1994) Potentiation of gamma-aminobutyric acidA receptor Cl-current correlates with in vivo anesthetic potency. J. Pharmacol. Exp. Ther. 270, 987–991.
Orser B. A., Wang L. Y., Pennefather P. S., and MacDonald J. F. (1994) Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons. J. Neurosci. 14, 7747–7760.
Wakamori M., Ikemoto Y., and Akaike N. (1991) Effects of two volatile anesthetics and a volatile convulsant on the excitatory and inhibitory amino acid responses in dissociated CNS neurons of the rat. J. Neurophysiol. 66, 2014–2021.
Lukatch H. S. and MacIver M. B. (1997) Voltage-clamp analysis of halothane effects on GABA(A fast) and GABA(A slow) inhibitory currents. Brain Res. 765, 108–112.
Lovinger D. M., Zimmerman S. A., Levitin M., Jones M. V., and Harrison N. L. (1993) Trichloroethanol potentiates synaptic transmission mediated by gamma-aminobutyric acid A receptors in hippocampal neurons. J. Pharmacol. Exp. Ther. 264, 1097–1103.
Hapfelmeier G., Schneck H., and Kochs E. (2001) Sevoflurane potentiates and blocks GABA-induced currents through recombinant alpha1beta2gamma2 GABAA receptors: implications for an enhanced GABAergic transmission. Eur. J. Anaesthesiol. 18, 377–383.
Jones M. V., Brooks P. A., and Harrison N. L. (1992) Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics. J. Physiol. 449, 279–293.
Ranft A., Kurz J., Deuringer M., et al. (2004) Isoflurane modulates glutamatergic and GABAergic neurotransmission in the amygdala. Eur. J. Neurosci. 20, 1276–1280.
Pittson S., Himmel A. M., and MacIver M. B. (2004) Multiple synaptic and membrane sites of anesthetic action in the CA1 region of rat hippocampal slices. BMC Neurosci. 5, 52.
MacIver M. B., Tanelian D. L., and Mody I. (1991) Two mechanisms for anesthetic-induced enhancement of GABAA-mediated neuronal inhibition. Ann. NY Acad. Sci. 625, 91–96.
Benkwitz C., Banks M. I., and Pearce R. A. (2004) Influence of GABAA receptor gamma2 splice variants on receptor kinetics and isoflurane modulation. Anesthesiology 101, 924–926.
Jurd R., Arras M., Lambert S., et al. (2003) General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J. 17, 250–252.
Berg-Johnsen J., and Langmoen I. A. (1993) Changes in inhibitory synaptic transmission induced by isoflurane studied in rat hippocampal slices. J. Neurosurg. Anesthesiol. 5, 36–40.
Antkowiak B. (1999) Different actions of general anesthetics on the firing patterns of neocortical neurons mediated by the GABA(A) receptor. Anesthesiology 91, 500–511.
Massaux A., Dutrieux G., Cotillon-Williams, N., Manunta Y., and Edeline J. M. (2004) Auditory thalamus bursts in anesthetized and non-anesthetized states: contribution to functional properties. J. Neurophysiol. 91, 2117–2134.
Nishikawa K. and MacIver M. B. (2000) Excitatory synaptic transmission mediated by NMDA receptors is more sensitive to isoflurane than are non-NMDA receptor-mediated responses. Anesthesiology 92, 228–236.
Berg-Johnsen J. and Langmoen I. A. (1992) The effect of isoflurane on excitatory synaptic transmission in the rat hippocampus. Acta. Anaesthesiol. Scand. 36, 350–355.
Dildy-Mayfield J. E., Eger E. I. 2nd, and Harris R. A. (1996) Anesthetics produce subunit-selective actions on glutamate receptors. J. Pharmacol. Exp. Ther. 276, 1058–1065.
Ouanounou A., Carlen P. L., and El-Beheiry H. (1998) Enhanced isoflurane suppression of excitatory synaptic transmission in the aged rat hippocampus. Br. J. Pharmacol. 124, 1075–1082.
Richards C. D. and Smaje J. C. (1976) Anaesthetics depress the sensitivity of cortical neurones to L-glutamate. Br. J. Pharmacol. 58, 347–357.
MacIver M. B. and Kendig J. J. (1989) Enflurane-induced burst discharge of hippocampal CA1 neurones is blocked by the NMDA receptor antagonist APV. Br. J. Anaesth. 63, 296–305.
Peoples R. W. and Weight F. F. (1998) Inhibition of excitatory amino acid-activated currents by trichloroethanol and trifluoroethanol in mouse hippocampal neurones. Br. J. Pharmacol. 124, 1159–1164.
Hara K. and Harris R. A. (2002) The anesthetic mechanism of urethane: the effects on neuro-transmitter-gated ion channels. Anesth. Analg. 94, 313–318, table of contents.
Weight F. F., Peoples R. W., Wright J. M., Lovinger D. M., and White G. (1993) Ethanol action on excitatory amino acid activated ion channels. Alcohol Alcohol Suppl. 2, 353–358.
Violet J. M., Downie D. L., Nakisa R. C., Lieb W. R., and Franks N. P. (1997) Differential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics. Anesthesiology 86, 866–874.
Hentschke H., Schwarz C., and Antkowiak B. (2005) Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and incease of GABAA receptor-mediated inhibition. Eur. J. Neurosci. 21, 93–102.
Scheller M., Bufler J., Hertle I., Schneck H. J., Franke C., and Kochs E. (1996) Ketamine blocks currents through mammalian nicotinic acetylcholine receptor channels by interaction with both the open and the closed state. Anesth. Analg. 83, 830–836.
Yamakura T., Chavez-Noriega L. E., and Harris R. A. (2000) Subunit-dependent inhibition of human neuronal nicotinic acetylcholine receptors and other ligand-gated ion channels by dissociative anesthetics keta-mine and dizocilpine. Anesthesiology 92, 1144–1153.
Lee B. H., Lamour Y., and Bassant M. H. (1991) Iontophoretic study of medial septal neurons in the unanesthetized rat. Neurosci. Lett. 128, 29–32.
Beckstead M. J., Phelan R., Trudell J. R., Bianchini M. J., and Mihic S. J. (2002) Anesthetic and ethanol effects on spontaneously opening glycine receptor channels. J. Neurochem. 82, 1343–1351.
Adachi Y. U., Watanabe K., Higuchi H., Satoh T., and Zsilla G. (2001) Halothane decreases impulse-dependent but not cytoplasmic release of dopamine from rat striatal slices. Brain. Res. Bull. 56, 521–524.
Tso M. M., Blatchford K. L., Callado L. F., McLaughlin D. P., and Stamford J. A. (2004) Stereoselective effects of ketamine on dopamine, serotonin and noradrenaline release and uptake in rat brain slices. Neurochem. Int. 44, 1–7.
Keita H., Henzel-Rouelle D., Dupont H., Desmonts J. M., and Mantz J. (1999) Halothane and isoflurane increase spontaneous but reduce the N-methyl-D-aspartate-evoked dopamine release in rat striatal slices: evidence for direct presynaptic effects. Anesthesiology 91, 1788–1797.
Larsen M., Haugstad T. S., Berg-Johnsen J., and Langmoen I. A. (1998) Effect of isoflurane on release and uptake of gamma-aminobutyric acid from rat cortical synaptosomes. Br. J. Anaesth. 80, 634–638.
Larsen M., Hegstad E., Berg-Johnsen J., and Langmoen I. A. (1997) Isoflurane increases the uptake of glutamate in synaptosomes from rat cerebral cortex. Br. J. Anaesth. 78, 55–59.
Lorrain D. S., Baccei C. S., Bristow L. J., Anderson J. J., and Varney M. A. (2003) Effects of ketamine and N-methyl-D-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 117, 697–706.
Tao R. and Auerbach S. B. (1994) Anesthetics block morphine-induced increases in serotonin release in rat CNS. Synapse 18, 307–314.
Detsch O., Vahle-Hinz C., Kochs E., Siemers M., and Bromm B. (1999) Isoflurane induces dose-dependent changes of thalamic somatosensory information transfer. Brain Res. 829, 77–89.
Angel A. and Gratton D. A. (1982) The effect of anaesthetic agents on cerebral cortical responses in the rat. Br. J. Pharmacol. 76, 541–549.
Shigenaga Y. and Inoki R. (1976) Effects of morphine and barbiturate on the SI and SII potentials evoked by tooth pulp stimulation of rats. Eur. J. Pharmacol. 36, 347–353.
Chapin J. K., Waterhouse B. D., and Woodward D. J. (1981) Differences in cutaneous sensory response properties of single somatosensory cortical neurons in awake and halothane anesthatized rats. Brain Res. Bull. 6, 63–70.
Montagne-Clavel J., Oliveras J. L., and Martin G. (1995) Single-unit recordings at dorsal raphe nucleus in the awake-anesthetized rat: spontaneous activity and responses to cutaneous innocuous and noxious stimulations. Pain 60, 303–310.
Patel I. M. and Chapin J. K. (1990) Ketamine effects on somatosensory cortical single neurons and on behavior in rats. Anesth. Analg. 70, 635–644.
Montagne-Clavel J. and Oliveras J. L. (1995) Does barbiturate anesthesia modify the neuronal properties of the somatosensory thalamus? A single-unit study related to nociception in the awake-pentobarbital-treated rat. Neurosci. Lett. 196, 69–72.
Shaw F. Z., Chen R. F., and Yen C. T. (2001) Dynamic changes of touch- and laser heat-evoked field potentials of primary somatosensory cortex in awake and pentobarbital-anesthetized rats. Brain Res. 911, 105–115.
Shimoji K., Fujioka H., Fukazawa T., Hashiba M., and Maruyama Y. (1984) Anesthetics and excitatory/inhibitory responses of midbrain reticular neurons. Anesthesiology 61, 151–155.
Cheung S. W., Nagarajan S. S., Bedenbaugh P. H., Schreiner C. E., Wang X., and Wong A. (2001) Auditory cortical neuron response differences under isoflurane versus pentobarbital anesthesia. Hear. Res. 156, 115–127.
Zbinden A. M., Maggiorini M., Petersen-Felix S., Lauber R., Thomson D. A., and Minder C. E. (1994) Anesthetic depth defined using multiple noxious stimuli during isoflurane/oxygen anesthesia. I. Motor reactions. Anesthesiology 80, 253–260.
Yen C. T. and Shaw F. Z. (2003) Reticular thalamic responses to nociceptive inputs in anesthetized rats. Brain Res. 968, 179–191.
Zhu M., Nehra D., Ackerman J. J. H., and Yablonskiy D. A. (2004) On the role of anesthesia on the body/brain temperature differential in rats. J. Therm. Biol. 29, 599.
Dickinson R., Lieb W. R., and Franks N. P. (1995) The effects of temperature on the interactions between volatile general anaesthetics and a neuronal nicotinic acetylcholine receptor. Br. J. Pharmacol. 116, 2949–2956.
Jenkins A., Franks N. P., and Lieb W. R. (1999) Effects of temperature and volatile anesthetics on GABA(A) receptors. Anesthesiology 90, 484–491.
Kiyatkin E. A. and Brown P. L. (2005) Brain and body temperature homeostasis during sodium pentobarbital anesthesia with and without body warming in rats. Physiol Behav 84, 563–570.
Brooks C. M., Koizumi K., and Malcolm J. L. (1955) Effects of changes in temperature on reactions of spinal cord. J. Neurophysiol. 18, 205–216.
Dyer R. S. and Boyes W. K. (1983) Hypothermia and chloropent anesthesia differentially affect the flash evoked potentials of hooded rats. Brain Res. Bull. 10, 825–831.
Bindman L. J., Lippold O. C., and Redfearn J. W. (1963) Comparison of the effects on electrocortical activity of general body cooling of the surface of the brain. Electroencephalogr. Clin. Neurophysiol. 15, 238–245.
Erickson C. A., Jung M. W., McNaughton B. L., and Barnes C. A. (1996) Contribution of single-unit spike waveform changes to temperature-induced alterations in hippocampal population spikes. Exp. Brain Res. 107, 348–360.
Moser E., Mathiesen I., and Andersen P. (1993) Association between brain temperature and dentate field potentials in exploring and swimming rats. Science 259, 1324–1326.
Andersen P. and Moser E. I. (1995) Brain temperature and hippocampal function. Hippocampus 5, 491–498.
Dingledine R., Dodd J., and Kelly J. S. (1980) The in vitro brain slice as a useful neurophysi ological preparation for intracellular recording. J. Neurosci. Methods 2, 323–362.
Dunwiddie T., Mueller A., and Basile A. (1983) The use of brain slices in central nervous system pharmacology. Fed. Proc. 42, 2891–2898.
Reid K. H., Edmonds H. L. Jr., Schurr A., Tseng M. T., and West C. A. (1988) Titfalls in the use of brain slices. Proc. Neurobiol. 31, 1–118.
Aitken P. G., Breese G. R., Dudek F. F., et al. (1995) Preparative methods for brain slices: a discussion. J. Neurosci. Methods 59, 139–149.
Richerson G. B. and Messer C. (1995) Effect of composition of experimental solutions on neuronal survival during rat brain slicing. Exp. Neurol 131, 133–143.
Crepel F., Dhanjal S. S., and Garthwaite J. (1981) Morphological and electrophysiological characteristics of rat cerebellar slices maintained in vitro. J. Physiol. 316, 127–138.
Bak I. J., Misgeld U., Weiler M., and Morgan E. (1980) The preservation of nerve cells in rat neostriatal slices maintained in vitro: a morphological study. Brain Res. 197, 341–353.
Burgoon P. W., Burry R. W., and Boulant J. A. (1997) Neuronal thermosensitivity and survival of rat hypothalamic slices in recording chambers. Brain Res. 777, 31–41.
Garthwaite J., Woodhams P. L., Collins M. J., and Balazs R. (1980) A morphological study of incubated slices of rat cerebellum in relatio nto postnatal age. Dev. Neurosci. 3, 90–99.
Fukuda A., Czurko A., Hida H., Muramatsu K., Lenard L., and Nishino H. (1995) Appearance of deteriorated neurons on regionally different time tables in rat brain thin slices maintained in physiological condition. Neurosci. Lett. 184, 13–16.
Whittingham T. S., Lust W. D., Christakis D. A., and Passoneau J. V. (1984) Metabolic stability of hippocampal slice preparations during prolonged incubation. J. Neurochem. 43, 689–696.
Whittingham T. S., Lust W. D., and Passonneau J. V. (1984) An in vitro model of ischemia: metabolic and electrical alterations in the hippocampal slice. J. Neurosci. 4, 794–802.
Schurr A., West C. A., and Rigor B. M. (1989) Electrophysiology of energy metabolism and neuronal function in the hippocampal slice preparation. J. Neurosci. Methods 28, 7–13.
Bingmann D. and Kolde G. (1982) PO2-proeiles in hipocampal slices of the guinea pig. Exp. Brain Res. 48, 89–96.
Kennedy R. T., Jones S. R., and Wightman R. M. (1992) Simultaneous measurement of oxygen and dopamine: coupling of oxygen consumption and neurotransmission. Neuroscience 47, 603–612.
Fujii T., Baumgartl H., and Lubbers D. W. (1982) Limiting section thickness of guinea pig olfactory cortical slices studied from tissue pO2 values and electrical activities. Pflugers Arch. 393, 83–87.
Misgeld U. and Frotscher M. (1982) Dependence of the viability of neurons in hippocampal slices on oxygen supply. Brain Res. Bull. 8, 95–100.
Zimmerman J. B., Kennedy R. T., and Wightman R. M. (1992) Evoled neuronal activity accompanied by transmitter release increases oxygen concentration in rat striatum in vivo but not in vitro. J. Cereb. Blood Flow Metab. 12, 629–637.
Taubenfeld S. M., Stevens K. A., Pollonini, G., Ruggiero J., and Alberini C. M. (2002) Profound molecular changes following hippocampal slice preparation: loss of AMPA receptor subunits and uncoupled mRNA/protein expression. J. Neurochem. 81, 1348–1360.
Shahbazian F. M., Jacobs M., and Lajtha A. (1986) Rates of amino acid incorporation into particulate proteins in vivo and in slices of young and adult brain. J. Neurosci. Res. 15, 359–366.
Shahbazian F. M., Jacobs M., and Lajtha A. (1986) Regional and cellular differences in rat brain protein synthesis in vivo and in slices during development. Int. J. Dev. Neurosci. 4, 209–215.
Dunlop D. S., van Elden W., and Lajtha A. (1975) Optimal conditions for protein synthesis in incubated slices of rat brain. Brain Res. 99, 303–318.
Dunlop D. S., van Elden W., and Lajtha A. (1977) Developmental effects on protein synthesis rates in regions of the CNS in vivo and in vitro. J. Neurochem. 29, 939–945.
Phillips L. L. and Steward O. (1988) Protein synthesis by rat hippocampal slices maintained in vitro. J. Neurosci. Res. 21, 6–17.
Thompson S. M., Masukawa L. M., and Prince D. A. (1985) Temperature dependence of intrinsic membrane properties and synaptic potentials in hippocampal CA1 neurons in vitro. J. Neurosci. 5, 817–824.
Dinkelacker V., Voets T., Neher E., and Moser T. (2000) The readily releasable pool of vesicles in chromaffin cells is replenished in a temperature-dependent manner and transiently overfills at 37 degrees C. J. Neurosci. 20, 8377–8383.
Pyott S. J. and Rosenmund C. (2002) The effects of temperature on vesicular supply and release in autaptic cultures of rat and mouse hippocampal neurons. J. Physiol. 539, 523–535.
Al-Hayani A. and Davies S. N. (2002) Effect of cannabinoids on synaptic transmission in the rat hippocampal slice is temperature-dependent. Eur. J. Pharmacol. 442, 47–54.
Asztely F., Erdemli G., and Kullmann D. M. (1997) Extrasynaptic glutamate spillover in the hippocampus: dependence on temperature and the role of active glutamate uptake. Neuron 18, 281–293.
Buldakova S., Dutova F., Ivlev S., and Weiss M. (1995) Temperature change-induced potentiation: a comparative study of facilitatory mechanisms in aged and young rat hippocampal slices. Neuroscience 68, 395–397.
McNaughton B. L., Shen J., Rao G., Foster T. C., and Barnes C. A. (1994) Persistent increase of hippocampal presynaptic axon excitability after repetitive electrical stimulation: dependence on N-methyl-D-aspartate receptor activity, nitric-oxide synthase, and temperature. Proc. Natl. Acad. Sci. USA 91, 4830–4834.
Watson P. L., Weiner J. L., and Carlen P. L. (1997) Effects of variations in hippocampal slice preparation protocol on the electrophysiological stability, epilpptogenicity and graded hypoxia responses of CA1 neurons. Brain Res. 775, 134–143.
Kirov S. A., Petrak L. J., Fiala J. C., and Harris K. M. (2004) Dendritic spines disappear with chilling but proliferate excessively upon rewarming of mature hippocampus. Neuroscience 127, 69–80.
Suter K. J., Smith B. N., and Dudek F. E. (1999) Electrophysiological recording from brain slices. Methods 10, 86–90.
Wenzel J., Otani S., Desmond N. L., and Levy W. B. (1994) Rapid development of somatic spines in stratum granulosum of the adult hippocampus in vitro. Brain Res. 656, 127–134.
Fiala J. C., Kirov S. A., and Feinberg M. D., et al. (2003) Timing of neuronal and glial ultrastructure disruption during brain slice preparation and recovery in vitro. J. Comp. Neurol. 465, 90–103.
Prosser R. A. and Gillette M. U. (1989) The mammalian circadian clock in the suprachiasmatic nuclei is reset in vitro by cAMF. J. Neurosci. 9, 1073–1081.
Timofeev I., Grenier F., Bazhenov M., Sejnowski T. J., and Steriade M. (2000) Origin of slow cortical oscillations in deafferented cortical slabs. Cereb. Cortex 10, 1185–99.
Inouye S. T. and Kawamura H. (1979) Persistence of circadian rhythmicity in a mammalian hypothalamic “island” containing the suprachiasmatic nucleus. Proc. Natl. Acad. Sci. USA 76, 5962–5966.
Timofeev I., Grenier F., and Steriade M. (2000) Impact of intrinsic properties and synaptic factors on the activity of neocortical networks in vivo. J. Physiol. Paris 94:343–355.
Kiyatki E. A., Brown P. L., and Wise R. A. (2002) Brain temperature fluctuation: a reflection of functional neural activation. Eur. J. Neurosci. 16, 164–168.
Kiyatkin E. A. and Mitchum R. D., Jr. (2003) Fluctuations in brain temperature during sexual interaction in male rats: an approach for evaluating neural activity underlying motivated behavior. Neuroscience 119, 1169–1183.
Kiyatkin E. A. and Brown P. L. (2004) Modulation of physiological brain hyperthermia by environmental temperature and impaired blood outflow in rats. Physiol. Behav. 83, 467–474.
Loewenstein Y., Mahon S., Chadderton P., et al. (2005) Bistability of cerebellar Purkinje cells modulated by sensory stimulation. Nat. Neurosci. 8, 202–211.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Windels, F. Neuronal activity. Mol Neurobiol 34, 1–25 (2006). https://doi.org/10.1385/MN:34:1:1
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/MN:34:1:1