Abstract
Changes in acetylcholine (ACh) release in the forebrain represent a critical step in the activation of larger neuronal circuits mediating cognitive functions. Therefore, the development of methods which allow the assessment of ACh release at a high temporal and spatial resolution is of immense significance for behavioral and cognitive neuroscience research. In this chapter, we review evidence from in vivo studies utilizing choline-sensitive microelectrodes for the detection of rapid changes in extracellular choline levels as a spatially discrete and sensitive measure of cortical cholinergic transmission. We then summarize empirical data from our lab based on studies involving electrochemical recordings and real-time monitoring of ACh release in animals performing a cued-appetitive response task. Phasic cholinergic activation in the prefrontal cortex, demonstrated by second-based increases in cholinergic transmission during behaviorally significant cues triggering reward approach, suggests that cholinergic transients encode specific information pertaining to the detection of attention-demanding cues. These findings indicate that cortical cholinergic transmission mediates defined cognitive operations which are contrary to the traditional description of cortical ACh as a slowly acting neuromodulator influencing different arousal states.
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References
Chiba AA, Bucci DJ, Holland PC, Gallagher M (1995) Basal forebrain cholinergic lesions disrupt increments but not decrements in conditioned stimulus processing. J Neurosci 15:7315–7322
Dalley JW, Theobald DE, Bouger P, Chudasama Y, Cardinal RN, Robbins TW (2004) Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-saporin-induced lesions of the medial prefrontal cortex. Cereb Cortex 14:922–932
McGaughy J, Dalley JW, Morrison CH, Everitt BJ, Robbins TW (2002) Selective behavioral and neurochemical effects of cholinergic lesions produced by intrabasalis infusions of 192 IgG-saporin on attentional performance in a five-choice serial reaction time task. J Neurosci 22:1905–1913
McGaughy J, Everitt BJ, Robbins TW, Sarter M (2000) The role of cortical cholinergic afferent projections in cognition: impact of new selective immunotoxins. Behav Brain Res 115:251–263
McGaughy J, Kaiser T, Sarter M (1996) Behavioral vigilance following infusions of 192 IgG-saporin into the basal forebrain: selectivity of the behavioral impairment and relation to cortical AChE-positive fiber density. Behav Neurosci 110:247–265
Muir JL, Dunnett SB, Robbins TW, Everitt BJ (1992) Attentional functions of the forebrain cholinergic systems: effects of intraventricular hemicholinium, physostigmine, basal forebrain lesions and intracortical grafts on a multiple-choice serial reaction time task. Exp Brain Res 89:611–622
Phillis JW (1968) Acetylcholine release from the cerebral cortex: its role in cortical arousal. Brain Res 7:378–389
Bartolini A, Pepeu G (1967) Investigations into the acetylcholine output from the cerebral cortex of the cat in the presence of hyoscine. Br J Pharmacol Chemother 31:66–73
Szerb JC (1967) Cortical acetylcholine release and electroencephalographic arousal. J Physiol 192:329–343
Pepeu G, Mantegazzini P (1964) Midbrain hemisection: effect on cortical acetylcholine in the cat. Science 145:1069–1070
Westerink BH, Cremers TI (2007) Handbook of microdialysis: methods, applications and perspectives, vol 16. Academic, London
Arnold HM, Burk JA, Hodgson EM, Sarter M, Bruno JP (2002) Differential cortical acetylcholine release in rats performing a sustained attention task versus behavioral control tasks that do not explicitly tax attention. Neuroscience 114:451–460
Dalley JW, McGaughy J, O’Connell MT, Cardinal RN, Levita L, Robbins TW (2001) Distinct changes in cortical acetylcholine and noradrenaline efflux during contingent and noncontingent performance of a visual attentional task. J Neurosci 21:4908–4914
Passetti F, Dalley JW, O’Connell MT, Everitt BJ, Robbins TW (2000) Increased acetylcholine release in the rat medial prefrontal cortex during performance of a visual attentional task. Eur J Neurosci 12:3051–3058
Cahill PS, Walker QD, Finnegan JM, Mickelson GE, Travis ER, Wightman RM (1996) Microelectrodes for the measurement of catecholamines in biological systems. Anal Chem 68:3180–3186
Michael DJ, Wightman RM (1999) Electrochemical monitoring of biogenic amine neurotransmission in real time. J Pharm Biomed Anal 19:33–46
Wightman RM, Robinson DL (2002) Transient changes in mesolimbic dopamine and their association with ‘reward’. J Neurochem 82:721–735
Phillips PE, Stuber GD, Heien ML, Wightman RM, Carelli RM (2003) Subsecond dopamine release promotes cocaine seeking. Nature 422:614–618
Daws LC, Toney GM, Gerhardt GA, Frazer A (1998) In vivo chronoamperometric measures of extracellular serotonin clearance in rat dorsal hippocampus: contribution of serotonin and norepinephrine transporters. J Pharmacol Exp Ther 286:967–976
Zahniser NR, Larson GA, Gerhardt GA (1999) In vivo dopamine clearance rate in rat striatum: regulation by extracellular dopamine concentration and dopamine transporter inhibitors. J Pharmacol Exp Ther 289:266–277
Staal RG, Mosharov EV, Sulzer D (2004) Dopamine neurons release transmitter via a flickering fusion pore. Nat Neurosci 7:341–346
Burmeister JJ, Pomerleau F, Palmer M, Day BK, Huettl P, Gerhardt GA (2002) Improved ceramic-based multisite microelectrode for rapid measurements of L-glutamate in the CNS. J Neurosci Methods 119:163–171
Pomerleau F, Day BK, Huettl P, Burmeister JJ, Gerhardt GA (2003) Real time in vivo measures of L-glutamate in the rat central nervous system using ceramic-based multisite microelectrode arrays. Ann NY Acad Sci 1003:454–457
Burmeister JJ, Palmer M, Gerhardt GA (2005) L-lactate measures in brain tissue with ceramic-based multisite microelectrodes. Biosens Bioelectron 20:1772–1779
Burmeister JJ, Gerhardt GA (2001) Self-referencing ceramic-based multisite microelectrodes for the detection and elimination of interferences from the measurement of L-glutamate and other analytes. Anal Chem 73:1037–1042
Burmeister JJ, Moxon K, Gerhardt GA (2000) Ceramic-based multisite microelectrodes for electrochemical recordings. Anal Chem 72:187–192
Garguilo MG, Michael AC (1996) Amperometric microsensors for monitoring choline in the extracellular fluid of brain. J Neurosci Methods 70:73–82
Oldenziel WH, Dijkstra G, Cremers TI, Westerink BH (2006) In vivo monitoring of extracellular glutamate in the brain with a microsensor. Brain Res 1118:34–42
Oldenziel WH, van der Zeyden M, Dijkstra G, Ghijsen WE, Karst H, Cremers TI, Westerink BH (2007) Monitoring extracellular glutamate in hippocampal slices with a microsensor. J Neurosci Methods 160:37–44
Day BK, Pomerleau F, Burmeister JJ, Huettl P, Gerhardt GA (2006) Microelectrode array studies of basal and potassium-evoked release of L-glutamate in the anesthetized rat brain. J Neurochem 96:1626–1635
Burmeister JJ, Pomerleau F, Huettl P, Gash CR, Werner CE, Bruno JP, Gerhardt GA (2008) Ceramic-based multisite microelectrode arrays for simultaneous measures of choline and acetylcholine in CNS. Biosens Bioelectron 23:1382–1389
Xin Q, Wightman RM (1997) Transport of choline in rat brain slices. Brain Res 776:126–132
Garguilo MG, Michael AC (1994) Quantitation of choline in the extracellular fluid of brain tissue with amperometric microsensors. Anal Chem 66:2621–2629
Burmeister JJ, Palmer M, Gerhardt GA (2003) Ceramic-based multisite microelectrode array for rapid choline measures in brain tissue. Anal Chim Acta 481:65–74
Parikh V, Pomerleau F, Huettl P, Gerhardt GA, Sarter M, Bruno JP (2004) Rapid assessment of in vivo cholinergic transmission by amperometric detection of changes in extracellular choline levels. Eur J Neurosci 20:1545–1554
Parikh V, Man K, Decker MW, Sarter M (2008) Glutamatergic contributions to nicotinic acetylcholine receptor agonist-evoked cholinergic transients in the prefrontal cortex. J Neurosci 28:3769–3780
Parikh V, Ji J, Decker MW, Sarter M (2010) Prefrontal beta2 subunit-containing and alpha7 nicotinic acetylcholine receptors differentially control glutamatergic and cholinergic signaling. J Neurosci 30:3518–3530
Parikh V, Sarter M (2006) Cortical choline transporter function measured in vivo using choline-sensitive microelectrodes: clearance of endogenous and exogenous choline and effects of removal of cholinergic terminals. J Neurochem 97:488–503
Rutherford EC, Pomerleau F, Huettl P, Stromberg I, Gerhardt GA (2007) Chronic second-by-second measures of L-glutamate in the central nervous system of freely moving rats. J Neurochem 102:712–722
Mitchell KM (2004) Acetylcholine and choline amperometric enzyme sensors characterized in vitro and in vivo. Anal Chem 76:1098–1106
Bruno JP, Gash C, Martin B, Zmarowski A, Pomerleau F, Burmeister J, Huettl P, Gerhardt GA (2006) Second-by-second measurement of acetylcholine release in prefrontal cortex. Eur J Neurosci 24:2749–2757
Giuliano C, Parikh V, Ward JR, Chiamulera C, Sarter M (2008) Increases in cholinergic neurotransmission measured by using choline-sensitive microelectrodes: enhanced detection by hydrolysis of acetylcholine on recording sites? Neurochem Int 52:1343–1350
Sarter M, Parikh V, Howe WM (2009) Phasic acetylcholine release and the volume transmission hypothesis: time to move on. Nat Rev Neurosci 10:383–390
Sarter M, Hasselmo ME, Bruno JP, Givens B (2005) Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection. Brain Res Brain Res Rev 48:98–111
Kozak R, Bruno JP, Sarter M (2006) Augmented prefrontal acetylcholine release during challenged attentional performance. Cereb Cortex 16:9–17
Himmelheber AM, Sarter M, Bruno JP (1997) Operant performance and cortical acetylcholine release: role of response rate, reward density, and non-contingent stimuli. Brain Res Cogn Brain Res 6:23–36
Himmelheber AM, Sarter M, Bruno JP (2000) Increases in cortical acetylcholine release during sustained attention performance in rats. Brain Res Cogn Brain Res 9:313–325
Parikh V, Kozak R, Martinez V, Sarter M (2007) Prefrontal acetylcholine release controls cue detection on multiple timescales. Neuron 56:141–154
Conner JM, Chiba AA, Tuszynski MH (2005) The basal forebrain cholinergic system is essential for cortical plasticity and functional recovery following brain injury. Neuron 46:173–179
Conner JM, Culberson A, Packowski C, Chiba AA, Tuszynski MH (2003) Lesions of the Basal forebrain cholinergic system impair task acquisition and abolish cortical plasticity associated with motor skill learning. Neuron 38:819–829
Parikh V, Sarter M (2008) Cholinergic mediation of attention: contributions of phasic and tonic increases in prefrontal cholinergic activity. Ann NY Acad Sci 1129:225–235
McGaughy J, Sarter M (1998) Sustained attention performance in rats with intracortical infusions of 192 IgG-saporin-induced cortical cholinergic deafferentation: effects of physostigmine and FG 7142. Behav Neurosci 112:1519–1525
Sarter M, Gehring WJ, Kozak R (2006) More attention must be paid: the neurobiology of attentional effort. Brain Res Rev 51:145–160
Hasselmo ME, Sarter M (2011) Modes and models of forebrain cholinergic neuromodulation of cognition. Neuropsychopharmacology 36:52–73
Blusztajn JK, Wurtman RJ (1983) Choline and cholinergic neurons. Science 221:614–620
Lockman PR, Allen DD (2002) The transport of choline. Drug Devel Ind Pharm 28:749–771
Ferguson SM, Bazalakova M, Savchenko V, Tapia JC, Wright J, Blakely RD (2004) Lethal impairment of cholinergic neurotransmission in hemicholinium-3-sensitive choline transporter knockout mice. Proc Natl Acad Sci USA 101:8762–8767
Apparsundaram S, Martinez V, Parikh V, Kozak R, Sarter M (2005) Increased capacity and density of choline transporters situated in synaptic membranes of the right medial prefrontal cortex of attentional task-performing rats. J Neurosci 25:3851–3856
Ferguson SM, Savchenko V, Apparsundaram S, Zwick M, Wright J, Heilman CJ, Yi H, Levey AI, Blakely RD (2003) Vesicular localization and activity-dependent trafficking of presynaptic choline transporters. J Neurosci 23:9697–9709
Ferguson SM, Blakely RD (2004) The choline transporter resurfaces: new roles for synaptic vesicles? Mol Interv 4:22–37
Atweh S, Simon JR, Kuhar MJ (1975) Utilization of sodium-dependent high affinity choline uptake in vitro as a measure of the activity of cholinergic neurons in vivo. Life Sci 17:1535–1544
Simon JR, Atweh S, Kuhar MJ (1976) Sodium-dependent high affinity choline uptake: a regulatory step in the synthesis of acetylcholine. J Neurochem 26:909–922
Collier B, Ilson D (1977) The effect of preganglionic nerve stimulation on the accumulation of certain analogues of choline by a sympathetic ganglion. J Physiol 264:489–509
Kessler PD, Marchbanks RM (1979) Choline transport is not coupled to acetylcholine synthesis. Nature 279:542–544
Sarter M, Parikh V, Howe WM (2009) nAChR agonist-induced cognition enhancement: integration of cognitive and neuronal mechanisms. Biochem Pharmacol 78:658–667
Howe WM, Ji J, Parikh V, Williams S, Mocaer E, Trocme-Thibierge C, Sarter M (2010) Enhancement of attentional performance by selective stimulation of alpha4beta2(*) nAChRs: underlying cholinergic mechanisms. Neuropsychopharmacology 35:1391–1401
Sarter M, Lustig C, Taylor SF (2012) Cholinergic contributions to the cognitive symptoms of schizophrenia and the viability of cholinergic treatments. Neuropharmacology 62(3):1544–53
Mesulam M, Shaw P, Mash D, Weintraub S (2004) Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-AD continuum. Ann Neurol 55:815–828
Potter AS, Newhouse PA, Bucci DJ (2006) Central nicotinic cholinergic systems: a role in the cognitive dysfunction in attention-deficit/hyperactivity disorder? Behav Brain Res 175:201–211
Sarter M, Parikh V (2005) Choline transporters, cholinergic transmission and cognition. Nat Rev Neurosci 6:48–56
Acknowledgements
The authors’ research was supported by PHS grants MH080426, MH080322, and AG092592.
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Parikh, V., Sarter, M. (2013). Forebrain Cholinergic Systems and Cognition: New Insights Based on Rapid Detection of Choline Spikes Using Enzyme-Based Biosensors. In: Marinesco, S., Dale, N. (eds) Microelectrode Biosensors. Neuromethods, vol 80. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-370-1_12
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DOI: https://doi.org/10.1007/978-1-62703-370-1_12
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