Abstract
Using electrophysiological techniques in the in vitro rat auditory cortex, we have examined how spontaneous acetylcholine (ACh) release modifies synaptic potentials mediated by glutamate and γ-aminobutyric acid (GABA). Single stimulus pulses to lower layer VI elicited in layer III a four-component (A-D) extracellular field response involving synaptic potentials mediated by glutamate and GABA. The cholinesterase inhibitor eserine (10–20 μM) or the cholinergic agonist carbachol (25–50 μM) depressed by 10–50% the glutamatergic components A and C, and the GABAergic components B and D. Atropine reversed the depressive effects of eserine and carbachol. A novel finding was that the degree of depression of component A varied inversely with stimulus intensity. However, during partial pharmacological antagonism of GABAA receptors, depression of A varied directly, not inversely, with stimulus intensity. Normally, then, depression of A is offset by reduced GABAergic inhibition of A. We also tested for differential depression of responses mediated by N-methyl-d-aspartate (NMDA) versus non-NMDA glutamate receptors. Following physiological and pharmacological isolation of the responses, eserine depressed the non-NMDA, but not the NMDA, receptor-mediated potential. Since the isolated NMDA potential still could be depressed by carbachol, the data suggested that activation of NMDA receptors may reduce spontaneous ACh release. In support of this, preincubation of slices in NMDA (10–20 μM) largely prevented eserine's, but not carbachol's, depression of components A and B.
These results permit three conclusions of relevance to cortical information processing: (1) spontaneous ACh release tonically depresses synaptic potentials mediated by glutamate and GABA; (2) ACh depresses responses to weak inputs to a greater degree than responses to strong inputs; (3) activation of NMDA receptors may “feed-back” to reduce ACh release, a mechanism that could place regulation of local ACh release under glutamatergic afferent control.
Similar content being viewed by others
References
Andreasen M, Lambert JDC, Jensen MS (1989) Effects of new non-N-methyl-d-aspartate antagonists on synaptic transmission in the in vitro rat hippocampus. J Physiol (Lond) 414:317–336
Aoki C, Kabak S (1992) Cholinergic terminals in the cat visual cortex: ultrastructural basis for interaction with glutamate-immunoreactive neurons and other cells. Visual Neurosci 8:177–191
Ashe JH, McKenna TM, Weinberger NM (1989) Cholinergic modulation of frequency receptive fields in auditory cortex. II. Frequency-specific effects of anticholinesterases provide evidence for a modulatory action of endogenous ACh. Synapse 4:44–54
Avoli M (1986) Inhibitory potentials in neruons of the deep layers of the in vitro neocortical slice. Brain Res 370:165–170
Baskerville KA, Chang HT, Herren P (1993) Topography of cholinergic afferents from the nucleus basalis of Meynert to representational areas of sensorimotor cortices in the rat. J Comp Neurol 335:552–562
Beaulieu C, Somogyi P (1991) Enrichment of Cholinergic synaptic terminals on GABAergic neurons and coexistence of immunoreactive GABA and choline acetyltransferase in the same synaptic terminals in the striate cortex of the rat. J Comp Neurol 304:666–680
Blanton MG, LoTurco JJ, Kriegstein AR (1989) Whole cell reording from neurons in slices of reptilian and mammalian cerebral cortex. J Neurosci Methods 30:203–210
Bode-Greuel KM, Singer W, Aldenhoff JB (1987) A current source density analysis of field potentials evoked in slices of visual cortex. Exp Brain Res 69:213–219
Cauller LJ, Connors BW (1994) Synaptic physiology of horizontal afferents to layer I in slices of rat SI neocortex. J Neurosci 14:751–762
Cole AE, Nicoll RA (1983) Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells. Science 221:1299–1301
Connors BW, Gutnick MJ, Prince DA (1982) Electrophysiological properties of neocortical neurons in vitro. J Neurophysiol 48:1302–1320
Connors BW, Malenka RC, Silva LR (1988) Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor-mediated responses in neocortex of rat and cat. J Physiol (Eond) 406:443–468
Cox CL, Metherate R, Weinberger NM, Ashe JH (1992) Synaptic potentials and amino acid antagonists in auditory cortex. Brain Res Bull 28:401–410
Cox CL, Metherate R, Ashe JH (1994) Modulation of cellular excitability in neocortex: muscarinic receptor and second messenger-mediated actions of acetylcholine. Synapse 16:123–136
Edeline J-M, Hars B, Maho C, Hennevin E (1994) Transient and prolonged facilitation of tone-evoked responses induced by basal forebrain stimulations in the rat auditory cortex. Exp Brain Res 97:373–386
Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14:60–67
Giovannini MG, Camilli F, Mundula A, Pepeu G (1994) Glutamatergic regulation of acetylcholine output in different brain regions: a microdialysis study in the rat. Neurochem Int 25:23–26
Hablitz JJ, Sutor B (1990) Excitatory postsynaptic potentials in rat neocortical neurons in vitro. III. Effects of a quinoxalinedione non-NMDA receptor antagonist. J Neurophysiol 64:1282–1290
Hagan JJ, Morris ROM (1988) The Cholinergic hypothesis of memory: a review of animal experiments. In: Iversen LL, Iversen SD, Snyder SH (eds) Psychopharmacology of the aging nervous system. Plenum, New York, pp 237–323
Hasegawa M, Kinoshita H, Amano M, Hasegawa T, Kameyama T, Nabeshima T (1993) MK-801 increases endogenous acetylcholine release in the rat parietal cortex: a study using brain microdialysis. Neurosci Lett 150:53–56
Hasselmo ME, Bower JM (1993) Acetylcholine and memory. Trends Neurosci 16:218–222
Hestrin S (1993) Different glutamate receptor channels mediate fast excitatory synaptic currents in inhibitory and excitatory cortical neurons. Neuron 11:1083–1091
Hicks TP, Kaneko T, Metherate R, Oka J-I, Stark CA (1991) Amino acids as transmitters of synaptic excitation in neocortical sensory processes. Can J Physiol Pharmacol 69:1099–1114
Hounsgaard J (1978) Presynaptic inhibitory action of acetylcholine in area CA1 of the hippocampus. Exp Neurol 62:787–797
Houser CR, Crawford GD, Salvaterra PM, Vaughn JE (1985) Immunocytochemical localization of choline acetyltransferase in rat cerebral cortex: a study of cholinergic neurons and synapses. J Comp Neurol 234:17–34
Hwa GGC, Avoli M, Oliver A, Villemure JG (1991) Bicucullineinduced epileptogenesis in the human neocortex maintained in vitro. Exp Brain Res 83:329–339
Jones EG, Peters A (1984) Functional properties of cortical Cells. Cereb Cortex 2:1–340
Jones K, Baughman RW (1988) NMDA- and non-NMDA receptor components of excitatory synaptic potentials recorded from cells in layer V of rat visual cortex. J Neurosci 8:3522–3534
Kaila K, Voipio J, Paalasmaa P, Pasternack M, Deisz RA (1993) The role of bicarbonate in GABAA receptor-mediated IPSPs of rat neocortical neurones. J Physiol (Lond) 464:273–289
Kharazia VN, Weinberg RJ (1994) Glutamate in thalamic fibers terminating in layer IV of primary sensory cortex. J Neurosci 14:6021–6032
Krnjevic K (1993) Central cholinergic mechanisms and function. Prog Brain Res 98:285–292
Luhmann HJ, Prince DA (1991) Postnatal maturation of the GABAergic system in rat neocortex. J Neurophysiol 65:247–263
McCormick DA, Prince DA (1986) Mechanism of action of acetylcholine in the guinea-pig cerebral cortex in vitro. J Physiol (Lond) 375:169–194
Mesulam M-M, Mufson EJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214:170–197
Metherate R, Ashe JH (1993a) Ionic flux contributions to neocortical slow waves and nucleus basalis-mediated activation: whole-cell recordings in vivo. J Neurosci 13:5312–5323
Metherate R, Ashe JH (1993b) Nucleus basalis stimulation facilitates thalamocortical synaptic transmission in rat auditory cortex. Synapse 14:132–143
Metherate R, Ashe JH (1994a) Facilitation of an NMDA receptormediated EPSP by paired-pulse stimulation in rat neocortex via depression of GABAergic IPSPs. J Physiol (Lond) 481:331–348
Metherate R, Ashe JH (1994b) Synaptic interactions involving acetylcholine, glutamate and GABA in rat neocortex. Soc Neurosci Abstr 20:1555
Metherate R, Weinberger NM (1990) Cholinergic modulation of responses to single tones produces tone-specific receptive field alterations in cat auditory cortex. Synapse 6:133–145
Metherate R, Cox CL, Ashe JH (1992) Cellular bases of neocortical activation: modulation of neural oscillations by the nucleus basalis and endogenous acetylcholine. J Neurosci 12:4701–4711
Montague PR, Gancayco CD, Winn MJ, Marchase RB, Friedlander MJ (1994) Role of NO production in NMDA receptor-mediated neurotransmitter release in cerebral cortex. Science 263:973–977
Moran J, Desimone R (1985) Selective attention gates visual processing in the extrastriate cortex. Science 229:782–784
Morrisett RA, Mott DD, Lewis DV, Swartzwelder HS, Wilson WA (1991) GABAB-receptor-mediated inhibition of the N-methyld-aspartate component of synaptic transmission in the rat hippocampus. J Neurosci 11:203–209
Mrzljak L, Levey AI, Goldman-Rakic PS (1993) Association of ml and m2 muscarinic receptor proteins with asymmetric synapses in the primate cerebral cortex: morphological evidence for cholinergic modulation of excitatory neurotransmission. Proc Natl Acad Sci USA 90:5194–5198
Pitler TA, Alger BE (1992) Cholinergic excitation of GABAergic interneurons in the rat hippocampal slice. J Physiol (Lond) 450:127–142
Posner MI, Dehaene S (1994) Attentional networks. Trends Neurosci 17:75–79
Raiteri M, Marchi M, Paudice P (1990) Presynaptic muscarinic receptors in the central nervous system. In: Kalsner S, Westfall TC (eds) Presynaptic receptors and the question of autoregulation of neurotransmitter release. NY Acad Sci, New York, pp 113–129
Rasmusson DD, Dykes RW (1988) Long-term enhancement of evoked potentials in cat somatosensory cortex produced by coactivation of the basal forebrain and cutaneous receptors. Exp Brain Res 70:276–286
Roger M, Arnault P (1989) Anatomical study of the connections of the primary auditory area in the rat. J Comp Neurol 287:339–356
Segal M (1983) Rat hippocampal neurons in culture: responses to electrical and chemical stimuli. J Neurophysiol 50:1249–1264
Shaw C, Teyler TJ (1982) The neural circuitry of the neocortex examined in the in vitro brain slice preparation. Brain Res 243:35–47
Steriade M, Buzsaki G (1990) Parallel activation of thalamic and cortical neurons by brainstem and basal forebrain cholinergic systems. In: Steriade M, Biesold D (eds) Brain cholinergic systems. Oxford University Press, Oxford, pp 3–62
Sutor B, Hablitz JJ (1989) EPSPs in rat neocortical neurons in vitro. I. Electrophysiological evidence for two distinct EPSPs. J Neurophysiol 61:607–620
Tremblay N, Warren RA, Dykes RW (1990) Electrophysiological studies of acetylcholine and the role of the basal forebrain in the somatosensory cortex of the cat. II. Cortical neurons excited by somatic stimuli. J Neurophysiol 64:1212–1222
Vidal C, Changeux J-P (1993) Nicotinic and muscarinic modulation of excitatory synaptic transmission in the rat prefrontal cortex in vitro. Neuroscience 56:23–32
Weinberger NM (1993) Learning-induced changes of auditory receptive fields. Curr Opin Neurobiol 3:570–577
White EL (1989) Cortical circuits. Birkhauser, Boston
Williams SH, Johnston D (1993) Muscarinic cholinergic inhibition of glutamatergic transmission. In: Dunwiddie TV, Lovinger DM (eds) Presynaptic receptors in the mammalian brain. Birkhauser, Boston, pp 27–41
Winer JA, Lame DT (1989) Populations of GABAergic neurons and axons in layer 1 of rat auditory cortex. Neuroscience 33:499–515
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Metherate, R., Ashe, J.H. Synaptic interactions involving acetylcholine, glutamate, and GABA in rat auditory cortex. Exp Brain Res 107, 59–72 (1995). https://doi.org/10.1007/BF00228017
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00228017