Functional organization of limbic brain structures during conditioned reflex activity in the dog

In experiments on 3 dogs it was shown that instrumental defensive conditioned reflex (CR) to electrical stimulation of the hippocampus is generalized within the limbic system (LS). The rate of generalization depended on the place of testing stimuli in LS. Stimulation of the medial parts of LS at the stage of stabilized initial reflex did not produce the generalized CRs, while they appeared distinctly in response to stimulation of the lateral parts of LS. In the process of elaboration of heterogeneous CRs (defensive and alimentary) to electrical stimulation of the hippocampus, generalized conditioned reactions from some brain structures appeared in both situations to the same degree while from other structures--with considerable differences. These data point to a possible participation in the genesis of the generalized CRs both of signal and reinforcing brain mechanisms.     

The effect of dorsal and ventral hippocampal lesions on short-term memory in cats]

The influence of lesion of the dorsal and ventral hippocampus on short-term memory was studied by the method of delayed conditioned reactions. It has been shown that after lesion of the dorsal hippocampus the delay considerably increases and that subsequent lesion of the ventral hippocampus completely eliminates delayed reactions. A conclusion has been drawn that the dorsal hippocampus has an inhibitory influence and the ventral hippocampus a facilitating effect on short-term memory. However the existence of a modulating effect does not imply that the hippocampus is a specific substrate of memory. A considerable part in the mechanism of memory is also played by other brain structures, which are activated together with the hippocampus. Particular importance is attached to activation of the bentromedial and lateral hypothalamus and the cortical associative areas.     

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.     

Projections of the posterior area of the hypothalamus to its medial,anterior, and lateral areas

The effect of stimulation of the lateral and medial supramammillary areas of the posterior hypothalamus on spontaneous single unit activity in the anterior, lateral, medial dorsal, and medial ventral areas of the hypothalamus was investigated in acute experiments on rabbits. Single stimulation of the medial area of the posterior hypothalamus evoked responses of 44% of neurons, whereas stimulation of the lateral area did so in only 35% of all neurons recorded. Repetitive stimulation led to an increase in the number of responding neurons (to 57% during stimulation of the lateral and 74% during stimulation of the medial supramammillary area). In response to repetitive stimulation of the medial supramammillary area, activating influences became predominant in all areas, whereas in response to stimulation of the lateral area, they became predominant in the medial, ventral, and lateral areas. The results are assessed from the standpoint of the role of the posterior hypothalamus in the regulation of adenohypophyseal functions.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 9, No. 4, pp. 377–381, July–August, 1977.     

Conditioned reflex analysis of functional connections between the hippocampus and limbic system structures

Instrumental defensive conditioned reflex elaborated in dogs to stimulation of the dorsal and ventral hippocampus, also appeared, due to generalization, in response to stimulation of a number of limbic structures. Two types of changes in the generalization effects (estimated by parameters of motor conditioned reaction) were observed in the course of conditioned reflex stabilization: enhancement (in response to stimulation of the lateral hypothalamus, lateral nucleus of septum, limbic cortex) and weakening toward complete disappearance (in response to stimulation of the medial nucleus of amygdala and medial hypothalamus). Manifestation of the generalization phenomenon from the brain structures, which are not involved initially into conditioned activity, suggests the existence of close functional connections between these structures and the hippocampus.     

Electrophysiologic study of hippocampo-hypothalamic connections in rabbits

Using the evoked potentials (EP) studies have been made on functional connections of different fields (CA1, CA3) of the dorsal hippocamp with phylogenetically different parts of the hypothalamus in rabbits. It was shown that during stimulation of both the field CA1 and the field CA3 of the hippocamp, the EP are widely present in nuclear structures of the posterior hypothalamus (supramammilary area, the posterior hypothalamic area, mammilary bodies). In the anterior hypothalamus (area preoptic medialis), the EP were recorded only during stimulation of the field CA1 in the dorsal hippocamp.     

Hypothalamic unit responses to impulses from the hippocampus and mesencephalic reticular formation

The effect of stimulation of the dorsal tegmentum mesencephali and dorsal hippocampus on spontaneous single unit activity of the retrochiasmal (RCA), lateral (LHA), medial dorsal (MHAd) and medial ventral (MHAv) hypothalamic regions was investigated in acute experiments on rabbits. During repetitive mesencephalic stimulation many more neurons were activated in all parts of the hypothalamus than during hippocampal stimulation. During mesencephalic stimulation more neurons were excited than inhibited in LHA, MHAd, and MHAv, but in RCA more were inhibited. During hippocampal stimulation spontaneous activity was inhibited in many more cells than during mesencephalic stimulation. Neurons on which convergence of impulses from the hippocampus and mesencephalon was observed numbered 25% in RCA, 39% in LHA, 46% in MHAd, and 29% in MHAv of the total number recorded. By their action (inhibitory or excitatory) on the hypothalamic neurons the mesencephalon and hippocampus were antagonistic in 60% of cases in RCA, 78% in LHA, and 61% in MHAd.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 6, No. 5, pp. 489–495, September–October, 1974.     

Functional Mapping of Dorsal and Median Raphe 5-Hydroxytryptamine Pathways in Forebrain of the Rat Using Microdialysis

Abstract: Recent neurochemical studies of the properties of 5-hydroxytryptamine (5-HT) pathways arising from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) have measured extracellular 5-HT in brain regions with reported preferential DRN or MRN 5-HT inputs. Here, we have tested whether electrical stimulation of the DRN and MRN releases 5-HT in rat forebrain regions in a pattern that fits the reported distribution of DRN/MRN pathways. The effect on extracellular 5-HT of electrical stimulation (5 Hz, 300 µA, 20 min) of the DRN, and then MRN, was determined in six regions of the anaesthetised rat. Stimulation of the DRN evoked a short-lasting but clear-cut release of 5-HT (+70–100%) in regions (frontal cortex, dorsal striatum, globus pallidus, and ventral hippocampus) reported to receive a 5-HT projection from the DRN. Regions receiving an MRN innervation (dorsal hippocampus, medial septum, and ventral hippocampus) released 5-HT (+70–100%) in response to MRN stimulation. Regions reported to receive a preferential DRN innervation (frontal cortex, dorsal striatum, and globus pallidus) did not respond to MRN stimulation. Of two regions (dorsal hippocampus and medial septum) reported to receive a preferential MRN innervation, one did not respond to DRN stimulation (dorsal hippocampus) although the other (medial septum) did. In summary, electrical stimulation of the DRN and MRN released 5-HT in a regionally specific pattern. With the exception of one region (medial septum), this pattern of release bears a strong relationship to the distribution of 5-HT projections from the DRN and MRN reported by anatomical studies. The combination of raphe stimulation with microdialysis may be a useful way to study the in vivo neurochemistry of DRN/MRN 5-HT pathways.     

Comparison of the mammalian and avian telencephalon from the perspective of gene expression data.

Pallial and subpallial morphological subdivisions of the mouse and chicken telencephalon were examined from the new perspective given by gene markers expressed in these territories during development. The rationale of this approach is that common gene expression patterns may underlie similar histogenetic specification and, consequently, comparable morphological nature. The nested expression domains of the genes Dlx-2 and Nkx-2.1 are characteristic for the subpallium (lateral and medial ganglionic eminences). Similar expression of these markers in parts of the mouse septum and amygdala suggests that such parts may be considered subpallial. The genes Pax-6, Tbr-1 and Emx-1 are expressed in the pallium. Complementary areas of the septum and amygdala shared expression of these genes, suggesting these are the pallial parts of these units. Differences in the relative topography of pallial marker genes also define different regions of the pallium, which can be partially traced into the amygdala. Importantly, there is evidence of a novel "ventral pallium" subdivision, which is a molecularly distinct pallial territory intercalated between the striatum and the lateral pallium. Its derivatives in the mouse apparently belong to the claustroamygdaloid complex. Chicken genes homologous sequence-wise to these mouse developmental genes are expressed in topologically comparable patterns during development. The avian subpallium -the paleostriatum- expresses Dlx-2 and Nkx-2.1; expression extends as well into the septum and anterior and medial parts of the archistriatum. The avian pallium expresses Pax-6, Tbr-1 and Emx-1 and also contains a distinct ventral pallium, formed by the neostriatum and ventral intermediate parts of the archistriatum. The lateral pallium comprises the hyperstriatum ventrale, overlying temporo-parieto-occipital corticoid layer and piriform cortex, plus dorsal intermediate and posterior archistriatum. The dorsal pallium includes the dorsal, intercalated and accessory hyperstriatum, plus the dorsolateral corticoid area. The medial pallium contains the hippocampus and parahippocampal area. A dorsal part of the septum shares pallial molecular markers. Gene markers thus suggest common sets of molecular developmental determinants in either pallial or subpallial domains of the mouse and chicken telencephalon, extending all the way from the posterior pole (amygdala) to the septum. Ventral pallial derivatives identified as claustroamygdaloid in the mouse correlate with avian neostriatum and parts of the archistriatum.     

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.     

Dorsal thalamic connections of the ventral lateral geniculate nucleus of rats

In order to understand better the organisation of the ventral lateral geniculate nucleus of the ventral thalamus, this paper has examined the patterns of connections that this nucleus has with various nuclei of the dorsal thalamus in rats. Injections of biotinylated dextran or cholera toxin subunit B were made into the parafascicular, central lateral, posterior thalamic, medial dorsal, lateral dorsal, lateral posterior, dorsal lateral geniculate, anterior, ventral lateral, ventrobasal and medial geniculate nuclei of Sprague-Dawley rats and their brains were processed using standard tracer detection methods. Three general patterns of ventral lateral geniculate connectivity were seen. First, the parafascicular, central lateral, medial dorsal, posterior thalamic and lateral dorsal nuclei had heavy connections with the parvocellular (internal) lamina of the ventral lateral geniculate nucleus. This geniculate lamina has been shown previously to receive heavy inputs from many functionally diverse brainstem nuclei. Second, the visually related dorsal lateral geniculate and lateral posterior nuclei had heavy connections with the magnocellular (external) lamina of the ventral lateral geniculate nucleus. This geniculate lamina has been shown by previous studies to receive heavy inputs from the visual cortex and the retina. Finally, the anterior, ventral lateral, ventrobasal and medial geniculate nuclei had very sparse, if any, connections with the ventral lateral geniculate nucleus. Overall, our results strengthen the notion that one can package the ventral lateral geniculate nucleus into distinct visual (magnocellular) and non-visual (parvocellular) components.     

Evoked potentials during the elaboration of a conditioned reflex to hippocampal stimulation in rats

In experiments on 9 rats, the study of evoked potentials (EPs) of the CA1 field of the dorsal hippocampus to stimulation of its symmetrical part serving as a signal of drinking conditioned reflex (CR) showed that during reflex elaboration, the amplitude of the main EP components significantly decreased; CR did not appear when the population spike (PS) was absent in the hippocampal response. PS always accompanying CR was not specific only of it, it was also recorded at other behavioural reactions. Changes of fascia dentata EPs in the process of CR elaboration to stimulation of its symmetrical part consisted in decrease of the initial negative wave and increase of the positive one. The obtained data point to a significant reconstruction of excitatory and inhibitory inputs to the hippocampus and fascia dentata under the influence of conditioned activity.     

Immunohistochemical mapping of galanin-like neurons in the rat central nervous system

Using an antiserum generated in rabbits against synthetic galanin (GA) and the indirect immunofluorescence method, the distribution of GA-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system (CNS) and a detailed stereotaxic atlas of GA-like neurons was prepared. GA-like immunoreactivity was widely distributed in the rat CNS. Appreciable numbers of GA-positive cell bodies were observed in the rostral cingulate and medial prefrontal cortex, the nucleus interstitialis striae terminalis, the caudate, medial preoptic, preoptic periventricular, and preoptic suprachiasmatic nuclei, the medial forebrain bundle, the supraoptic, the hypothalamic periventricular, the paraventricular, the arcuate, dorsomedial, perifornical, thalamic periventricular, anterior dorsal and lateral thalamic nuclei, medial and central amygdaloid nuclei, dorsal and ventral premamillary nuclei, at the base of the hypothalamus, in the central gray matter, the hippocampus, the dorsal and caudoventral raphe nuclei, the interpeduncular nucleus, the locus coeruleus, ventral parabrachial, solitarii and commissuralis nuclei, in the A1, C1 and A4 catechaolamine areas, the posterior area postrema and the trigeminal and dorsal root ganglia. Fibers were generally seen where cell bodies were observed. Very dense fiber bundles were noted in the septohypothalamic tract, the preoptic area, in the hypothalamus, the habenula and the thalamic periventricular nucleus, in the ventral hippocampus, parts of the reticular formation, in the locus coeruleus, the dorsal parabrachial area, the nucleus and tract of the spinal trigeminal area and the substantia gelatinosa, the superficial layers of the spinal cord and the posterior lobe of the pituitary. The localization of the GA-like immunoreactivity in the locus coeruleus suggests a partial coexistence with catecholaminergic neurons as well as a possible involvement of the GA-like peptide in a neuroregulatory role.     

Effect of destruction of the septum and hippocampus on the shuttle-box avoidance conditioning of the rat

Total destruction of the septum, the dorsal hippocampus (DH), or the lesion of the DH combined with that of the medial septal nucleus in rats was shown to facilitate elaboration of conditioned avoidance responses in a shuttle-box due to an increase of general excitability of the animals, and to cause significant impairment of internal inhibition formation. Lesions of the medial or the lateral septal nuclei as well as a combined lesion of the DH and the lateral septal nucleus had no significant effect on conditioning and internal inhibition elaboration. Therefore the septo-hippocampal connections had different functional directions during active defensive behaviour.     

Features of the formation of conditioned secretory reflexes in response to the stimulation of different areas of the caudate nucleus of the dog

Properties were studied of elaboration of conditioned alimentary secretory reflexes to threshold electric stimulation of the caudate nucleus in dogs. The rate of formation of such a reflex and its magnitude were considerably lower than in reflexes elaborated to distant stimuli. Latencies were longer; dynamics of conditioned and unconditioned secretory reactions was similar to that of reflexes to a weak stimulus--light. The motor component of the conditioned alimentary reaction, as a rule, was absent. Characteristics were revealed of formation of alimentary reflexes to stimulation of the dorsal and ventral parts of the head and body of the caudate nucleus.     

Anatomico-functional approach to the mechanisms of memory: analysis by deoxyglucose of the limbic activation induced by electric stimulation of the mouse entorhinal cortex

Previous behavioral studies using post-training electrical stimulation of the brain have suggested that the lateral entorhinal cortex (LEC) is involved in mnemonic processes. In an attempt to characterize in vivo the neural pathways activated by LEC stimulation, regional patterns of uptake of 14C-2-deoxy-D-glucose (2-DG) were assessed in BALB/c mouse brain. The animals were implanted with a bipolar electrode in the LEC and a catheter in the jugular vein. In addition, four animals received an electrolytic lesion of the perforant path (PP) in order to disconnect the LEC from the hippocampus. The LEC was stimulated at subconvulsive intensity for 5 min. before and 30 min. after an injection of 2-DG. Stimulation of the LEC produced significant increases in 2-DG radioactivity in the hippocampus (dentate gyrus, CA3, CA1), subiculum and pre-subiculum. Demonstrable labelling was found in brain areas, beyond the hippocampal formation: piriform cortex, amygdala, cingulate cortex, Diagonal Band of Broca, the medial and lateral septal nuclei and the medial forebrain bundle. After PP lesion, the metabolic activity disappeared ipsilaterally in subiculum, dorsal part of the hippocampus, in some thalamic nuclei and in mammillary bodies, but all other extra-hippocampal labelling was unchanged. These data considered along with our previous behavioral results, suggest that LEC stimulation may act on mnemonic processes by the recruitment of cortical and subcortical extra-hippocampal structures (e.g. amygdala and cingulate cortex) directly or indirectly connected to the entorhinal cortex.     

Analysis of the effects of electrical stimulation of certain limbic structures

It has been established that stimulation of the structures of the limbic system (hippocampus, amygdaloid complex, septum) and the medial nucleic of the thalamus of rabbits in conditions of free behavior elicits four basic types of behavioral reactions: arousal, orientation-investigatory, aggressive-defensive and various epileptiform (convulsive) reactions. Activation of behavior, i.e., arousal and the orientation-investigatory reaction, constantly appear on stimulation of the unspecific thalamic nuclei. The aggressive-defense reaction is elicited by stimulating the nuclei of the amygdaloid complex of the ventral part of the hippocampus and the ventromedial nuclei of the thalamus. The epileptiform reactions are most readily reproduced on stimulation of the amygdaloid complex and the ventral part of the hippocampus. The threshold for the appearance of discharges of the aftereffect is very low. The latter are more sustained on stimulation of the basolateral part of the amygdala and the ventral part of the hippocampus. In rabbits as compared with higher animals the discharges on stimulation rapidly spread not only to the limbic system but also to the reticular formation and the neocortex.Kharkov Medical Institute. Translated from Neirofiziologiya, Vol. 1, No. 2, pp. 194–201, September–October, 1969.     

Functional role of the dorsal and ventral hippocampus in defensive behavior in the rat

Bilateral electrolytic lesions of the dorsal hippocampus of white rats were shown to facilitate elaboration of a conditioned response of active avoidance of pain shock in a shuttle-box. The lesions of the ventral hippocampus had no effect on conditioning. The ventral hippocampal lesions led to a complete failure to form differential inhibition. In rats with the dorsal hippocampal lesions an acquisition of partial (up to 60 per cent) discrimination of stimuli was possible. The differences in avoidance conditioning and elaboration of differential inhibition in rats with the dorsal and ventral hippocampal lesions are supposed to be caused by the changes of general excitability and emotional state of animals as well as by a specific role of the ventral hippocampus in memory consolidation.     

Effect of stimulation of field CA3 in the dorsal hippocampus on the motor polarization dominant in rabbits

The influence was studied of the stimulation of the CA3 field of the dorsal hippocampus on the course of motor polarization dominant created by the action of the direct current on the rabbit's cortical sensorimotor area. It is shown that hippocampus stimulation by 1 mA current (0.5 ms, 100 Hz, 0.2 s) against the background of the dominant optimum elicits its inhibition. It is manifested in depression of the motor "dominant" reaction of the forelimb to testing stimuli and in abolition of coherent connections of theta-range electrical activity of the sensorimotor cortex and CA3 field of the dorsal hippocampus. On the contrary, the hippocampus stimulation by a weak current (30-50 mcA, 0.5 ms, 30 Hz, 0.2 s) during optimum dominant reinforces it, eliciting a movement of the "dominant" limb. Against the background of an unstable dominant it provides for its activation and stabilization and recovers the dominant in the following days during its extinction.     

Distribution of gastrin-releasing peptide immunoreactivity in the brain of the collared dove (Streptopelia decaocto)

The distribution of immunoreactivity after applying an antibody against gastrin-releasing peptide (GRP) was studied in the brain of the collared dove (Streptopelia decaocto). In the forebrain GRP-immunoreactive (GRP-ir) cells were found in the hyperstriatum accessorium, medial and lateral parts of the neostriatum, corticoidea dorsolateralis and temporoparieto-occipitalis areas, hippocampus, pre- and parahippocampal areas and prepiriform cortex. In the brainstem, GRP-ir cells were restricted mainly to the substantia nigra and ventral tegmental nucleus. Areas with densely packed GRP-ir clusters of varicosities were the medial intermediate hyperstriatum ventrale and lateral septal nucleus; dense GRP-ir neuropil was found in the parolfactory lobe, and in the dorsal half of the intermediate and caudal archistriatum. The ventral lamina medullaris contained many GRP-ir fibers. Forebrain areas devoid of immunoreactivity were the basal nucleus, ectostriatum, rostral archistriatum, most of the paleostriatum augmentatum and the lateral bed nucleus of the stria terminalis. Moderate densities of GRP-ir elements were found in the other telencephalic areas and further in, among others, the preoptic and hypothalamic region, ventral area of Tsai, cerulean nuclei, parabrachial complex, dorsal glossopharyngeal and vagus motor nuclei and medial nuclei of the solitary complex. The observations are compared with data from the literature and the implications for the definition of specific centers within the avian brain are discussed, with emphasis on systems with a role in visceral and motivational functions and in learning.