Corticofugal influences on the neurons of different regions of the hypothalamus

Responses of the neurons of the lateral and ventromedial hypothalamic regions (HL andHvm, respectively), as well as of the area of the dorsal hypothalamus (aHd) and the projection region of the medial forelimb bundle (MFB), evoked by stimulation of the proreal cortex (field 8), cingular cortex (field 24), pyriform lobula (periamigdalar cortex), and hippocampus (CA3) were studied in acute experiments on cats under ketamine anesthesia. Distributions of the latent periods of the responses recorded from hypothalamic neurons at stimulation of the above cortical structures were analyzed. The responses were classified into primary excitatory and primary inhibitory. Stimulation of the proreal gyrus evoked four times more excitatory responses than inhibitory responses. With stimulation of the cingular gyrus, the ratio of excitatory/inhibitory responses was 1.5∶1. Stimulation of the pyriform cortex evoked activatory and inhibitory responses with a similar probability. With hippocampal stimulation, inhibitory responses appeared two times more frequently than excitatory reactions. The hypothalamus was found to be a zone of wide convergence: one-half of all responding neurons in theHL andHvm responded to stimulations of two or more tested cortical zones. In 26% of the cells, only excitatory convergence was observed, while in 10% only inhibitory convergence was found; 21% of the cells revealed mixed convergence.     

Characteristics of responses of preoptic neurons to presentation of serial cortical stimuli

Responses of neurons of the medial (MPO) and lateral (LPO) preoptic region (RPO) and adjacent hypothalamic structures to serial stimuli (6–300/sec) of the prefrontal (area 8) and cingulate (area 24) cortex, piriform lobe (periamygdaloid cortex — RPA), and hippocampus (area CA3) were investigated in acute experiments on cats under ketamine anesthesia. Four main types of responses were found: excitatory, inhibitory, excitatory on-off effect, and inhibitory on-off effect. With the use of stimuli with increasing frequencies, the direction of the response remained constant, only its intensity changed. Neurons responding to presentation of serial stimuli were localized mainly in the central part of the MPO and basal part of the LPO, where the most pronounced foci of convergence were observed. During serial stimulation of cortical structures, inhibitory responses occurred considerably more often than excitatory (ratio 3.4:1). The presence of a gradient of inhibition was established from new to old (in a phylogenetic respect) brain formations in a number of stimulated structures. In the case of stimulating the neocortex (proreal gyrus), the predominance of inhibitory responses over excitatory was minimum (1.7:1); it increased (1.9:1) in the case of stimulating the intermediate cortex (cingulate gyrus), still more (4.5:1) under conditions of stimulating the paleocortex (periamygdaloid cortex), and in the case of stimulating the archicortex (10.2:1).A. M. Gorky Medical Institute, Ukrainian Ministry of Health, Donetsk. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 720–731, November–December, 1991.     

Unitary responses of the hypothalamic nuclei to stimulation of the frontobasal neocortex

Unitary responses in the hypothalamic nuclei to stimulation of the frontobasal zones of the cortex (proreal, orbito-insular, and basal temporal regions) were studied. Cortico-thalamic connections were found to possess definite topical organization: the orbito-frontal zones of the cortex have a more marked effect on unit activity of the hypothalamic nuclei than the basal temporal cortex. Antidromic activation, during stimulation of a particular region of the cortex, of neurons excited orthodromically by stimulation of another cortical structure, enables a number of neuronal circuits functioning within the forebrain to be distinguished. The first circuit includes the orbital gyrus, preoptic zone, and proreal gyrus. The second circuit has the same cortical components as the first, but its relay in the hypothalamus takes place in the region of the mamillary bodies. The third circuit is represented by the basal temporal cortex, lateral hypothalamus, and prefrontal cortex.M. Gor'kii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 10, No. 1, pp. 44–53, January–February, 1978.     

Corticofugal influences on pontine unit activity

Unit responses of the nuclei pontis (NP) and reticular pontine nuclei (RPN) to stimulation of the frontobasal cortex (proreal, orbital, and basal temporal regions) and of the dorsal hippocampus were studied in cats. Stimulation of the various cortical structures was found to induce phasic and (less frequently) tonic responses in neurons of NP and RPN. The main type of unit response in RPN was primary excitation, whereas in NP it was primary inhibition. The largest number of responding neurons in the pontine nuclei was observed to stimulation of the proreal gyrus. In the cerebro-cerebellar relay system neurons of the reticular tegmental nucleus and ventromedial portion of NP showed the highest ability to respond. In the oral and caudal reticular pontine nuclei the regions of predominant influence of cortical structures were located in zones of these nuclei where neurons with rostral and (to a lesser degree) caudal projections were situated.M. Gorkii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 12, No. 4, pp. 358–367, July–August, 1980.     

Electrophysiological investigation of cortico-hypothalamic relations in cats

Projections of different parts of the orbito-frontal cortex, the basal temporal cortex, and the hippocampus on hypothalamic nuclei were studied by recording focal responses in acute experiments on cats anesthetized with pentobarbital and chloralose. The proreal gyrus was shown to have local projections in the latero-dorsal zones of the preoptic region, in the rostral parts of the medial forebrain bundle, and also in the region of the lateral and posterior hypothalamus with the mammillary bodies. The orbital gyrus projects mainly to the latero-dorsal portions of the forebrain bundle, the latero-ventral part of the preoptic region, and the region of the lateral and latero-dorsal hypothalamic nuclei; projections from the orbital gyrus are relatively diffuse in character. The basal temporal cortex has diffuse projections in the central part of the preoptic region, in the latero-ventral parts of the medial forebrain bundle, and in the lateral mammillary body. No marked foci of activity were found in the hypothalamic structures during hippocampal stimulation. Diffuse projections of the hippocampus were traced in the ventral part of the preoptic region and the ventral regions of the medial forebrain bundle, and also in the lateral hypothalamus and in the lateral mammillary nucleus.A. M. Gor'kii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 8, No. 4, pp. 358–365, July–August, 1976.     

Interaction of influences from the auditory and somatosensory afferent systems on neurons of the primary auditory cortex

In experiments on anesthetized cats, 80 neurons of the primary auditory cortex (A1) were studied. Within the examined neuronal population, 66 cells (or 82.5%) were monosensory units, i.e., they responded only to acoustic stimulations (sound clicks and tones); 8 (10.1%) neurons responded to acoustic stimulation and electrocutaneous stimulation (ECS); the rest of the units (7.4%) were either trisensory (responded also to visual stimulation) or responded only to non-acoustic stimulations. In the A1 area, neurons responding to ECS with rather short latencies (15.6–17.0 msec) were found. ECS usually suppressed the impulse neuronal responses evoked by sound clicks. It is concluded that somatosensory afferent signals cause predominantly an inhibitory effect on transmission of an acoustic afferent volley to the auditory cortex at a subcortical level; however, rare cases of excitatory convergence of acoustic and somatosensory inputs toA1 neurons were observed.     

Response activity of different areas of the associative region of the cerebral cortex in the cat

In cats we have simultaneously (monopolarly) recorded the responses in different parts of the associative cortex (ac) (motor cortex, proreal, orbital, anterior marginal, and mid-part of the suprasylvian gyri) appearing for different peripheral stimulations (stimulation of the skin of the forelimbs, a light flash and a sound click). In all the regions of the ac associative responses (ar) almost identical in configuration appeared to all the peripheral stimulations. The ar of the orbitofrontal and the motor cortex differed from the ar of the suprasylvian gyrus in the shorter latent period and greater stability. In each part of the ac we found the same focus of maximum activity for all the peripheral stimulations. For paired stimulations of the same and different modalities the greatest stability in relation to the blocking influence due to the conditioning stimulation characterized the ar which appeared in response to skin stimulation in the orbitofrontal cortex and the ar which appeared in the suprasylvian gyrus on exposure to a light flash. It is assumed that in the orbitofrontal cortex an efferent discharge is formed in response to pulses of different sensory modality whereas in the suprasylvian gyrus there is only sensory integration. Some aspects of afferent convergence are discussed.Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 2, No. 2, pp. 126–139, March–April, 1970.     

Comparative study of effect of cortical nucleus of amygdala and pyriform cortex on activity of bulbar respiratory neurons in cats

Comparative microelectrophysiological study of character and peculiarities of effects of the cortical nucleus of amygdala and of the periamygdalar area of pyriform cortex on impulse activity was performed on the same single functionally identified respiratory medullar neurons. A high reactivity of bulbar respiratory neurons to stimulation is established in both studied limbic structures. There is established the qualitatively different character of their response reactions at stimulation of the cortical amygdala nucleus and the periamygdalar cortex. The cortical amygdala nucleus has been shown to produce both facilitating and inhibitory effects (with predominance of the activating one) on activity of medullar respiratory neurons (without topographical orderliness). The effect of periamygdalar cortex at stimulation of various parts was characterized by topographic differentiation. The suppressing reactions of neurons in the majority of cases were recorded at stimulation of the rostral area of periamygdalar cortex, whereas the excitatory reactions-at stimulation of its caudal part. Functional organization of respiratory control of the studied limbic system structures is discussed.     

Electrophysiological analysis of corticofugal influences on preoptic neurons

Evoked potential (EPs) and responses of the medial (MPO) and lateral (LPO) preoptic region (RPO) and adjacent structures of the hypothalamus to stimulation of the prefrontal (area 8) and cingulate (area 24) cortex, piriform lobe (periamygdaloid cortex), and hippocampus (area CA3) were investigated in acute experiments on cats under ketamine anesthesia. The most pronounced EPs were observed in the RPO after stimulating the piriform and cingulate cortex. A close relation was found between neuronal responses and EP components. The majority of neurons responding to stimulation of various cortical structures were localized in the LPO, where primarily excitatory responses dominate. The MPO contained somewhat fewer neurons responding to cortical stimulation, and the dominant response here was primarily inhibitory. The ratio of inhibitory and excitatory responses in the LPO was 0.6:1 and in the MPO 5.8:1. Primarily in-inhibitory responses dominated also in the LPO zone adjacent to the bed nucleus stria terminalis (BST) and primarily excitatory in the region surrounding the supraoptic nucleus (SO) (respective ratios 4.9:1 and 0.7:1). The RPO is a broad convergence zone, where 3/4 of the neurons responded to stimuli of two and more cortical regions.A. M. Gorky Medical Institute, Ukrainian Minstry of Health, Donetsk. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 709–719, November–December, 1991.     

Modulation of neuronal impulse activity of the anterior hypothalamus as a functional basis of the mechanisms underlying hypothalamic control

We examined the neuronal activity of hypothalamic neurons in acute experiments on cats under ketamine anesthesia. Using glass microelectrodes, we extracellularly recorded the impulse activity (IA) of neurons of the anterior hypothalamus in the absence of controlled influences (background IA, BIA) and after stimulation of evolutionary heterogeneous zones of the brain cortex projecting to the hypothalamus (hippocampal CA3 area, pyriform, cingular, and proreal gyri). Electrical 5-sec-long stimuli were applied with frequencies of 12, 30, or 100 sec⁻¹. In another experimental series, we recorded changes in the IA of hypothalamic neurons induced by visceral stimuli (heating or cooling by 7°C of the foot pad, cooling of the body of the animal, and infusions of 5% glucose, 0.2% NaCl, 3.0% NaCl, or phenylephrine in the carotid artery), modeling in such a way shifts of the constants of homeostasis within physiological limits. We also compared the parameters of neuronal BIA and stimulation-influenced IA in equal epochs of the analysis and classified the types of BIA. About 50% of the cells of the total studied sampling of hypothalamic neurons responded by a considerable modulation of their BIA with a significant change in the frequency in the course of and after stimulations of the above-mentioned modalities. In some neurons after cortical or visceral stimulation, a significant transformation of the temporal structure of the IA with no changes in the mean frequency occurred. We hypothesize that stimulation-induced transformation of the IA pattern with preservation of the mean discharge frequency can be one of the modes of encoding of information necessary for triggering of one efferent reaction or another, which are controlled by the hypothalamus. Examination of the BIA parameters of subcortical neurons, as well as comparison of the parameters of such an activity with the localization of cells and with the modality of stimulation that leads to modification of the IA, should allow one to reveal reasons for the formation and modification of the IA on neurons of the anterior hypothalamus. Since functional peculiarities of the neurons correlate with their BIA pattern, such data can provide an insight into the functional bases of the neurophysiological mechanisms underlying regulatory functions of the hypothalamus. Neirofiziologiya/Neurophysiology, Vol. 37, Nos. 5/6, pp. 463–474, September–December, 2005.     

Comparative study of effects of cortical nucleus of amygdala and pyriform cortex on activity of bulbar respiratory neurons in cats

Comparative microelectrophysiological study of character and peculiarities of effects of the cortical nucleus of amygdala and of the periamygdalar area of pyriform cortex on impulse activity was performed on the same single functionally identified respiratory medullar neurons. A high reactivity of bulbar respiratory neurons on stimulation is established in both studied limbic structures. There is established the qualitatively different character of their response reactions at stimulation of the cortical amygdala nucleus and the periamygdalar cortex. The cortical amygdala nucleus has been shown to produce on the activity of medullar respiratory neurons both facilitating and inhibitory action with predominance of the activating one (without topographical orderliness). The effect of periamygdalar cortex at stimulation of various parts was characterized by topographic differentiation. The suppressing reactions of neurons in the majority of cases were recorded at stimulation of the rostral area of periamygdalar cortex, whereas the excitatory reactions--at stimulation of its caudal part. Functional organization of respiratory control of the studied limbic system structures is discussed.     

Interaction of the monoaminergic and opioidergic brain systems in the course of nociceptive and antinociceptive reactions in cats

Nociceptive responses were evoked in cats by electrical transcutaneous stimulation of the forepaw or electrical stimulation of respective brain structures; these responses could be modulated (intensified or suppressed) by combined electrical stimulation of different brain structures or by neurochemical influences upon these structures. Intensification of nociceptive responses was observed after stimulation of the noradrenergic orP-ergic systems localized in the ventral zone of the central gray (vl SGC) and the structures monosynaptically connected with the latter: the posterior and lateral hypothalamic nuclei (Hp andHl) and preoptic region (RPO). Similar effects were induced by suppression of the serotoninergic system concentrated within the dorsolateral central gray (dl SGC), dorsal raphe nucleus (Rd), and closely related structures: the ventromedial, dorsomedial, and paraventricular hypothalamic nuclei (Hvm, Hdm, andHpv), septum (Sep), basolateral amygdalar nucleus (Am bl), fields 3–4 of the hippocampus (CA3–4), and cingular cortex (GC). Suppression of the serotoninergic system resulted in a decrease in the levels of functioning of the met-enkephalin- and β-endorphinergic systems and facilitation of theP-ergic system. Moderation of nociceptive responses, i.e., an analgesic effect, was observed after either stimulation of the serotonin-, met-enkephalin-, and β-endorphinergic systems localized in thedl SGC, Rd, Hvm, Hdm, Sep, Am bl, CA3–4, andGC, or suppression of the noradrenergic system. The latter influence resulted in inhibition of theP-ergic system and a rise in the functional activity of the met-enkephalin- and β-endorphinergic systems. The composition of two antagonistic brain systems, nociceptive and antinociceptive, is considered. The antinociceptive system includes serotonin-, met-enkephalin-, and β-endorphinergic elements. Leu-enkephalin is a nonspecific activator of the met-enkephalin-, β-endorphin-, andP-ergic systems. The nociceptive system consists of thevl SGC, Hp, Hl, andRPO, while the antinociceptive system includes thedl SGC, Rd, Hvm, Hdm, Hpv, Sep, Am dl, CA3–4, andGC.     

Possible mechanisms of the anterior limbic cortex influence on the neuron activity of the vago-solitary complex

In ananesthetized cats, neurons of the nucleus of the tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNV) revealed phasic excitatory responses to separate single vagal and cortical stimuli. Stimulation of the anterior limbic cortex combined with vagal stimulation resulted in inhibitory or excitatory modification of the vagal induced responses of the NTS and DMNV neurons. The data obtained suggest that complete inhibitory effects are related to general cortical mechanisms of control of the functional state of the brain stem visceral neurons. Selective inhibition of the vagal induced responses by limbic cortex stimulation is due to particular cortical mechanisms of the visceral sensory transmission control via the NTS neurons.     

Convergence of corticofugal impulses on pontine neurons

Convergence of corticofugal impulses in reticular and intrinsic pontine nuclei during stimulation of the frontobasal cortex (proreal, posterior orbital, and basal temporal regions) and also of the dorsal hippocampus was studied in acute experiments on cats anesthesized with a mixture of pentobarbital and chloralose. Three foci of convergence of corticofugal impulses were found in these structures: one in the reticular formation and two in the intrinsic nuclei—in their medial and lateral portions. Neurons with an excitatory type of response were shown to predominate in the reticular formation and neurons with an inhibitory or mixed type of response of neurons activated antidromically by stimulation of one brain region and synaptically during stimulation of another, that the pontine nuclei play an integrative role in the functional unification of structures of the frontobasal zones of the neocortex and hippocampus.M. Gor'kii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 12, No. 5, pp. 472–480, September–October, 1980.     

Mechanisms of corticofugal control of the activity of “vagal” viscerosensory neurons in theNucleus tractus solitarii

In experiemnts on cats under chloralose-nembutal anesthesia, we studied viscerosensory neurons in thenucl. tractus solitarii identified by their responses to stimulation of then. vagus. The responses of these cells to stimulation of the secondary sensorimotor cortex (zoneS2) and dorsal regions of field 25 of the limbic cortex (DLC) were recorded. A substantial part of the “vagal” viscerosensory units demonstrated convergent properties and responded toS2 and DLC stimulations by phasic responses. The short latencies of these responses were indicative of oligosynaptic and, in some cases, even monosynaptic transmission of corticofugal influences on a considerable part of such neurons. Using paired stimulation allowed us to demonstrate that the effects of stimulation of the visceral afferent fiber undergo long-lasting suppression exerted by descending corticofugal volleys. The mechanisms of cortical control of the activity of bulbar viscerosensory neurons are discussed.     

Unit responses of the reticular and ventral anterior thalamic nuclei of cats to orbitofrontal cortical stimulation

Responses of 98 neurons of the reticular (R) and 72 neurons of the ventral anterior (VA) thalamic nuclei to stimulation of various zones of the orbitofrontal cortex were investigated in acute experiments on cats immobilized with D-tubocurarine. Not all zones of this cortex were found to be connected equally closely with R and VA. Most of the R (82.7%) and VA (66.7%) neurons responded to stimulation of the proreal gyrus, and fewest (37.3 and 48.9%, respectively) to stimulation of the posterior orbital gyrus. Among the responding neurons, 85.2–86.3% of R cells and 78.2–81.2% of VA cells were excited by cortical stimulation and the rest were inhibited. Excitation was expressed as the appearance of a single spike or of discharges of varied duration in response to each stimulus. The latent period of the spike responses varied from 0.5 to 55.0 msec and the minimal latent period of the discharges was 0.8 msec and its maximal value over 500 msec. The spike frequency in the discharge was 120–250/sec. Unit responses consisting of spikes with a latent period of under 1.3 msec and, it is assumed, some of the responses with a latent period of under 4.0 msec were antidromic. The axons of some R and VA neurons were shown to form branches terminating in different zones of the orbitofrontal cortex.     

Postsynaptic Reactions in Somatosensory Cortex Neurons Activated by Stimulation of Nociceptors: Modulation upon Stimulation of the Central Grey, <Emphasis Type="Italic">Locus Coeruleus</Emphasis>, and <Emphasis Type="Italic">Substantia Nigra</Emphasis>

In experiments on cats, we studied the effects of electrical stimulation of the cerebral central grey (CG), locus coeruleus (LC), and substantia nigra (SN) on postsynaptic processes evoked by nociceptive volleys in somatosensory cortex neurons. Nineteen cells activated exclusively by stimulation of nociceptors (intense stimulation of the dental pulp) and 26 cells activated by both nociceptive and non-nociceptive (near-threshold) stimulations of the n. infraorbitalis and thalamic nucl. ventroposteromedialis (VPM) were intracellularly recorded (nociceptive and convergent cortical neurons, respectively). In neurons of both groups, stimulation of both nociceptive afferents and the VPM evoked complex responses having on EPSP-spike-IPSP patterns (duration of IPSPs about 200-300 msec). Electrical stimulation of the СG, which per se could activate the examined cortical neurons, induced prolonged suppression of synaptic responses evoked by stimulation of nociceptors; maximum inhibition was observed at 600- to 800-msec-long conditioning–test intervals. A certain parallelism was observed between the conditioning effects of СG stimulation and effects of systemic introduction of morphine. Isolated stimulations of the LC and SN by short high-frequency pulse series evoked primary complex EPSPs in a part of the examined cortical neurons, while high-amplitude IPSPs (up to 120 msec long) were observed in other units. Independently of the type of the primary response, conditioning stimulations of the LC and SN induced long-lasting (several seconds) suppression of synaptic responses evoked in cortical neurons by stimulation of nociceptive inputs. Mechanisms of modulating influences coming from opioidergic, noradrenergic, and dopaminergic cerebral systems to neurons of the somatosensory cortex activated upon excitation of high-threshold (nociceptive) afferent inputs are discussed.     

Responses of the neurons of the cortical secondary auditory area to acoustic and non-acoustic stimuli in cats

The responses of the cortical secondary auditory area (AII) to the non-acoustic stimuli (electrical stimulation of the skin in the vibrissae area and light flash) and their combination with acoustic stimulation (sound click or tone) were studied in experiments on cats anesthetized by kalipsol using extra- and intracellular recording. Of the total number of neurons, 69% of the units generating spike responses to the acoustic stimulation responded to the non-acoustic stimulation too. The responses to the modal-nonspecific stimulation, as a rule, were weak and variable; they were mostly represented by a tonic change in the neuronal discharge frequency. The nonspecific stimulation evoked primary excitatory and inhibitory postsynaptic potentials in 77% and 20% of the examined neurons, respectively. We found that synaptic effects of the nonspecific and specific stimulations interact with each other, ensuring considerable modulation of the latter (mostly a significant facilitation resulting from the EPSP summation and suppression of an inhibitory component of the response to acoustic stimulation). Possible participation of the midbrain reticular formation in the transmission of the modal-nonspecific influences to the cortical neurons is considered; stimulation of this structure evoked responses similar to those evoked by the modal-nonspecific sensory stimuli.Neirofiziologiya/Neurophhysiology, Vol. 26, No. 5, pp. 356–364, September–October, 1994.     

Unit activity in the posterior sigmoid and proreal gyri of the cat cortex during bemegride administration

Unit activity was studied in the posterior sigmoid and proreal gyri of the cat cortex in response to photic, acoustic, and somatic stimulation. The animals were first anesthetized with pentobarbital and, after recovery, were given intravenous injections of bemegride (β-ethyl-β-methylglutarimide) and immobilized with diplacin [1, 3-di(β-platyneciniumethoxy)-benzene hydrochloride]. The state of the preparation used was similar to the state of waking animals as regards the characteristics of its unit activity. Unit responses of the proreal gyrus were chiefly modally nonspecific and consisted of brief suppression of spontaneous activity for 100–200 msec. Neurons of the posterior sigmoid gyrus were characterized by much greater modal specificity and variety of types of responses to stimuli of different modalities. Comparison of the characteristics of unit activity in these parts of the neocortex suggests that the frontal cortex in cats is still a highly unspecialized structure.     

Excitatory and Inhibitory Effects of A1 and A2A Adenosine Receptor Activation on the Electrically Evoked [3H]Acetylcholine Release from Different Areas of the Rat Hippocampus

Abstract: The modulation by adenosine analogues and endogenous adenosine of the electrically evoked release of [³H]acetylcholine ([³H]ACh) was compared in subslices of the three areas of the rat hippocampus (CA1, CA3, and dentate gyrus). The mixed A₁/A₂ agonist 2-chloroadenosine (CADO; 2–10 µM) inhibited, in a concentration-dependent manner, the release of [³H]ACh from the three hippocampal areas, being more potent in the CA1 and CA3 areas than in the dentate gyrus. The inhibitory effect of CADO (5 µM) on [³H]ACh release was prevented by the A₁ antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 50 nM) in the three hippocampal areas and was converted in an excitatory effect in the CA3 and dentate gyrus areas. The A_2A agonist CGS-21680 (30 nM) produced a greater increase of the evoked release of [³H]ACh in the CA3 than in the dentate gyrus areas, whereas no consistent effect was found in the CA1 area or in the whole hippocampal slice. The excitatory effect of CGS-21680 (30 nM) in the CA3 area was prevented by the adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (10 µM). Both adenosine deaminase (2 U/ml) and DPCPX (250 nM) increased the evoked release of [³H]ACh in the CA1 and CA3 areas but not in the dentate gyrus. The amplitude of the effect of DPCPX and adenosine deaminase was similar in the CA1 area, but in the CA3 area DPCPX produced a greater effect than adenosine deaminase. It is concluded that the electrically evoked release of [³H]ACh in the three areas of the rat hippocampus can be differentially modulated by adenosine. In the CA1 area, only A₁ inhibitory receptors modulate ACh release, whereas in the CA3 area, both A_2A excitatory and A₁ inhibitory adenosine receptors modulate ACh release. In the dentate gyrus, both A₁ inhibitory and A_2A excitatory adenosine receptors are present, but endogenous adenosine does not activate them.