Summary
The effects of cholinergic basal forebrain lesions on the activity of the glutamatergic and GABAergic systems were investigated in the rat frontal cortex and hippocampus. Bilateral quisqualic acid injections in the nucleus basalis magnocellularis (NBM) at the origin of the main cholinergic innervation to the neocortex induced a cholinergic deficit in the cerebral cortex 15 days later, as shown by the marked selective decrease in cortical choline acetyltransferase (CAT) activity observed. Concurrent alterations in the kinetic parameters of high affinity glutamate uptake consisting mainly of a decrease in the V max were observed in the cerebral cortex. These changes presumably reflect a decreased glutamatergic transmission and provide support for the hypothesis that cortical glutamatergic neurons may undergo the influence of cholinergic projections from the NBM. Surprisingly, similar alterations in the glutamate uptake process were found to occur at hippocampal level in the absence of any significant change in the hippocampal cholinergic activity. These data indicate that the NBM may contribute to regulating hippocampal glutamatergic function without interfering with the hippocampal cholinergic innervation that mainly originates in the medial septal area-diagonal band (MSA-DB) complex. No change in parameters of GABAergic activity, namely the glutamic acid decarboxylase (GAD) activity and high affinity GABA uptake, were observed in any of the structures examined. In a second series of experiments involving bilateral intraventricular injections of AF 64 A, marked survival time-dependent decreases in CAT and high affinity choline uptake activities but no significant change in the high affinity glutamate uptake rate were observed in the hippocampus. No significant change in either parameters of cholinergic activity or in the glutamate uptake was concurrently observed in the cerebral cortex. The GABAergic activity was again unaffected whatever the survival time and the structure considered. Taken as a whole, these data suggest that basal forebrain projections originating in the NBM may play a major role in regulating glutamatergic but not GABAergic function in both the cerebral cortex and the hippocampus; whereas the glutamatergic and GABAergic activities in these two structures may not be primarily under the influence of the cholinergic projections from the MSA-DB complex.
Similar content being viewed by others
Abbreviations
- NBM :
-
nucleus basalis magnocellularis
- MSA-DB :
-
medial septal area-diagonal band
- CAT :
-
choline acetyltransferase
- GAD :
-
glutamic acid decarboxylase
- GABA :
-
gamma-aminobutyric acid
References
Albers RW, Brady R (1959) The distribution of glutamic decarboxylase in the nervous system of the rhesus monkey. J Biol Chem 234: 926–928
Beckstead RM (1978) Afferent connections of the entorhinal area in the rats as demonstrated by retrograde cell-labelling with horseradish peroxidase. Brain Res 152: 249–264
Brashear HR, Zaborsky L, Heimer L (1986) Distribution of GABAergic and cholinergic neurons in the rat diagonal band. Neuroscience 17: 439–451
Casamenti F, Di Patre PL, Bartolini L, Pepeu G (1986) Unilateral and bilateral nucleus basalis lesions: differences in neurochemical and behavioural recovery. Neuroscience 24: 209–215
Chrobak JJ, Hanin I, Schmechel DE, Walsh TJ (1988) AF 64 A induced memory impairments: behavioural neurochemical and histological correlates. Brain Res 463: 107–117
Davies P, Maloney AJR (1976) Selective loss of central cholinergic neurons in Alzheimer's disease. Lancett ii: 1403
Dunnett SB, Whishaw IQ, Jones GH, Bunch ST (1987) Behavioural, biochemical and histochemical effects of different neurotoxic amino acids injected into nucleus basalis magnocellularis of rats. Neuroscience 20: 653–669
Eckenstein FP, Baughman RN, Quinn J (1988) An anatomical study of cholinergic innervation in the rat cerebral cortex. Neuroscience 25: 457–474
Emson PC (1979) Distribution of putative neurotransmitters in the neocortex. Neuroscience 4: 1–30
Flint RS, Murphy JM, Calkins PM, Mac Bride WJ (1985) Monoamine, aminoacid and cholinergic interactions in slices of rat cerebral cortex. Brain Res Bull 15: 197–202
Fonnum F (1975) Radiochemical assays for choline acetyltransferase and acetylcholinesterase. In: Marks N, Rodnight R (eds) Research methods in neurochemistry, vol 3. Plenum Press, New York, pp 253–274
Hebb CO, Krnjevic K, Silver A (1963) Effect of undercutting on the acetylcholinesterase and choline acetyltransferase activity in the cat's cerebral cortex. Nature 198: 692
Hohmann CF, Wenk GL, Lowenstein P, Brown ME, Coyle JT (1987) Age related recurrence of basal forebrain lesion-induced cholinergic deficits. Neurosci Lett 82: 253–259
Johnston MV, Mac Kinney M, Coyle JT (1981) Neocortical cholinergic innervation: a description of extrinsic and intrinsic components in the rat. Exp Brain Res 43: 159–172
Juliano SL, Ma W, Eslin D (1991) Cholinergic depletion prevents expansion of topographic maps in somatosensory cortex. Proc Natl Acad Sci 88: 780–784
Karnovsky MJ (1964) The localization of cholinesterase activity in rat cardiac muscle by electron microscopy. J Cell Biol 23: 217–231
Koliatos VE, Martin LJ, Walker LC, Richardson RT, De Long MR, Price DL (1988) Topographic, non collateralized basal forebrain projections to amygdala, hippocampus, and anterior cingulate cortex in the rhesus monkey. Brain Res 463: 133–139
König FRJ, Klippel RA (1967) The rat brain: a stereotaxic atlas of the forebrain and lower parts of the brainstem. Williams and Wilkins, Baltimore
Kosaka T, Tauchi M, Dahl JL (1988) Cholinergic neurons containing GABA-like and/or glutamic acid decarboxylase-like immunoreactivities in various brain regions of the rat. Exp Brain Res 70: 605–617
Krettek JE, Price JL (1974) Projections from the amygdala to the perirhinal and entorhinal cortices and the subiculum. Brain Res 71: 150–154
Kuhar MJ, Murrin LC (1978) Sodium-dependant, high affinity choline uptake. J Neurochem 30: 15–21
Lamarca MV, Fibiger HC (1984) Deoxyglucose uptake and choline acetyltransferase activity in cerebral cortex following lesions of the nucleus basalis magnocellularis. Brain Res 307: 366–369
Lamour Y, Dutar P, Jobert A (1982) Excitatory effect of acetylcholine on different types of neurons in the first somatosensory neocortex of the rat: laminar distribution and pharmacological characteristics. Neuroscience 7: 1483–1494
Lehmann J, Nagy JI, Atmadja S, Fibiger HC (1980) The nucleus basalis magnocellularis: the origin of a cholinergic projection to the neocortex of the rat. Neuroscience 5: 1161–1174
Leventer SM, Wulfert E, Hanin I (1987) Time course of ethylcholine aziridinium ion (AF 64 A) induced cholinotoxicity in vivo. Neuropharmacology 26: 361–365
Levey AI, Wainer BH, Rye DB, Mufson EJ, Mesulam MM (1984) Choline acetyltransferaseimmunoreactive neurons intrinsic to rodent cortex and distinction from acetylcholinesterase-positive neurons. Neuroscience 13: 341–353
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Mesulam MM, Mufson EJ, Wainer RH, Levey AI (1983) Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (CH 1–Ch 6). Neuroscience 10: 1185–1201
Morris RGM, Anderson E, Lynch GS, Baudry M (1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptors antagonist, AP 5. Nature 319: 774–776
Murray CL, Fibiger HC (1985) Learning and memory deficits after lesions of the nucleus basalis magnocellularis: reversal by physostigmine. Neuroscience 14: 1025–1032
Nagai T, Kimura H, Maeda T, Mc Geer PL, Peng F, Mc Geer EG (1982) Cholinergic projections from the basal forebrain of rat to the amygdala. J Neurosci 2: 513–520
Nieoullon A, Dusticier N (1981) Glutamate decarboxylase distribution in discrete motor nuclei in the cat brain. J Neurochem 37: 202–209
Nieoullon A, Kerkerian L, Dusticier N (1983) Presynaptic dopaminergic control of high affinity glutamate uptake in the striatum. Neurosci Lett 95: 31–36
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd ed. Academic Press, London
Pedata F, Loconte G, Sorbi S, Marconcini-Pepeu I, Pepeu G (1982) Changes in high affinity choline uptake in rat cortex following lesions of the magnocellular forebrain nuclei. Brain Res 233: 359–367
Perry EK (1986) The cholinergic hypothesis—ten years on. Br Med Bull 42: 63–69
Robbins TW, Everitt BJ, Ryan CN, Marston HM, Jones GH, Paget KJ (1989) Comparative effects of quisqualic acid and ibotenic acid induced lesions of the substantia innominata and globus pallidus on the acquisition of a conditional visual discrimination: differential effects on cholinergic mechanisms. Neuroscience 28: 337–352
Szerb JC, Fine A (1989) Is glutamate a co-transmitter in cortical cholinergic terminals? Effects of nucleus basalis lesion and of presynaptic muscarinic agents. Brain Res 515: 214–218
Smith G (1988) Animal models of Alzheimer's disease: experimental cholinergic denervation. Brain Res Rev 13: 103–118
Stone TW (1972) Cholinergic mechanisms in the rat somatosensory cerebral cortex. J Physiol (Lond) 225: 485–499
Storm-Mathisen J (1977) Glutamic acid and excitatory nerve endings: reduction of glutamic acid uptake after axotomy. Brain Res 120: 379–386
Vacca LL, Rosario SL, Zimmerman EA, Tomashefsky P, Po-Ying NG, Hsu KC (1975) Application of immunoperoxidase techniques to localize horseradish peroxidase tracer in the central nervous system. J Histochem Cytochem 23: 208–215
Van Hoesen GN, Pandya DN (1975) Some connections of the entorhinal (area 28) and perirhinal (area 35) cortices of the rhesus monkey I. Temporal lobe afferents. Brain Res 95: 1–24
Wenk GL, Olton DS (1984) Recovery of neocortical choline acetyltransferase activity following ibotenic acid injection into the nucleus basalis of Meynert in rats. Brain Res 293: 184–186
Wenk GL, Cribbs B, Mac Call L (1984) Nucleus basalis magnocellularis: optimal coordinates for selective reduction of choline acetyltransferase in frontal neocortex by ibotenic acid injections. Exp Brain Res 56: 335–340
Woolf NJ, Butcher LL (1982) Cholinergic projections to the basolateral amygdala: a combined Evans-blue and acetylcholinesterase analysis. Brain Res Bull 8: 751–763
Woolf NJ, Eckenstein F, Butcher LL (1984) Cholinergic systems in the rat brain. I. projections to the limbic telencephalon. Brain Res Bull 13: 751–784
Author information
Authors and Affiliations
Additional information
Laboratoire associé à l'Université Aix-Marseille II
Rights and permissions
About this article
Cite this article
Reine, G., Samuel, D., Nieoullon, A. et al. Effects of lesion of the cholinergic basal forebrain nuclei on the activity of glutamatergic and GABAergic systems in the rat frontal cortex and hippocampus. J. Neural Transmission 87, 175–192 (1992). https://doi.org/10.1007/BF01245364
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01245364