Showing papers on "GABAergic published in 1987"

Activation of NMDA receptors blocks GABAergic inhibition in an in vitro model of epilepsy

Abstract: The application of tetanic electrical stimuli to the stratum radiatum fibre pathway in the hippocampus in vitro produces an NMDA (N-methyl-D-aspartate) receptor-dependent enhancement of synaptic efficacy. Repeated application of such stimuli produces a progressive enhancement of synaptic efficacy leading to the genesis of spontaneous and stimulation-evoked epileptiform discharges. We have used this in vitro approach to explore the cellular mechanisms which underlie the kindling model of epilepsy. Kindling of the stratum radiatum fibre pathway in vitro induced a progressive, long-lasting reduction of both spontaneous and stimulation-evoked GABAergic (gamma-aminobutyric acid-mediated) inhibitory postsynaptic potentials (i.p.s.ps). The reduction of i.p.s.ps by kindling was associated with a profound decrease in the sensitivity of CA1 pyramidal neurons to ionophoretically applied GABA and an increase in sensitivity to NMDA. The reduction of i.p.s.ps and GABA sensitivity was prevented by kindling in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-APV). These results demonstrate that kindling-like stimulus patterns produce a reduction of GABAergic inhibition in the hippocampus resulting from a stimulus-induced postsynaptic activation of NMDA receptors. The modulation of GABAergic inhibition by NMDA receptors may cause the synaptic plasticity which underlies the kindling model of epilepsy.

Delayed transneuronal death of substantia nigra neurons prevented by gamma-aminobutyric acid agonist.

Abstract: In an investigation of the mechanism by which brain lesions result in delayed degeneration of neurons remote from the site of injury, neurons within the caudate nucleus of rats were destroyed by local injection of the excitotoxin ibotenic acid. Treatment resulted in the rapid degeneration of the striatonigral pathway including projections containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and delayed transneuronal death of neurons in the substantia nigra pars reticulata. The distribution of nigral cell loss corresponded to the loss of GABAergic terminals. Neuronal death was prevented by long-term intraventricular infusion of the GABA agonist muscimol. Delayed transneuronal degeneration may be produced by neuronal disinhibition consequent to loss of inhibitory inputs. Replacement of inhibitory transmitters by suitable drugs may prevent some forms of delayed neuronal death.

Early loss of somatostatin neurons in dentate hilus after cerebral ischemia in the rat precedes CA-1 pyramidal cell loss.

Abstract: Somatostatin (SS)- and cholecystokinin (CCK)-immunopositive cell somata in the rat hippocampus were quantitated at day 1, 2, 3 and 4 after cerebral ischemia. A significant (P<0.01) 60%–80% loss of hilar and CA-3c SS neurons took place. No CCK neurons were lost. Damage to SS neurons was significant on the second postischemic day and preceded the delayed loss of CA-1 neurons. We speculate that loss of SS neurons, which presumably innervate the inhibitory GABAergic (γ-aminobutyric acid) interneurons, may induce hyperactivity stimulating the Ca-1 neurons to death.

GABA immunoreactive neurons in rat visual cortex

Abstract: An antiserum to γ-aminobutyric acid (GABA) was used in a light and electron microscopic immunocytochemical study to determine the morphology and distribution of GABA-containing neurons in the rat visual cortex and to ascertain whether all classes of nonpyramidal neurons in this cortex are GABAergic. The visual cortex used for light microscopy was prepared in such a way that the antibody penetrated completely through tissue sections, and in these sections large numbers of GABA immunoreactive neurons were apparent. The labeled neurons could be identified as being either multipolar, bitufted, bipolar, or horizontal neurons. In layers II through Via, GABA immunostained cells were distributed uniformly and accounted for approximately 15% of all neurons, but in layer I all neurons appeared to be immunostained. Electron microscopy of GABA immunostained visual cortex prepared to ensure good fine structural preservation confirmed the presence in layers II through Via of numerous immunoreactive bipolar neurons, both small and large varieties, as well as multipolar and bitufted neurons. Additionally, electron microscopy reveals that astrocytes are frequently GABA immunoreactive. From a correlated light and electron microscopic evaluation of neurons in GABA immunostained visual cortex, it was possible to confirm which kinds of neurons are GABAergic and what proportion of the neuronal population they represent. Thus, from an analysis of some 950 neurons, it was found that pyramidal neurons were never immunoreactive and that except for 20% of the bipolar cell population, all examples of other types of nonpyramidal neurons encountered in this material were GABA immunoreactive.

Cholinergic innervation of hippocampal GAD‐ and somatostatin‐immunoreactive commissural neurons

Abstract: This study describes the cholinergic innervation of chemically defined nonpyramidal neurons in the hilar region of the rat hippocampus. Cholinergic terminals were identified by immunocytochemistry employing a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme, and the avidin-biotin-peroxidase (ABC) technique. Nonpyramidal neurons in the hilar region were characterized by immunostaining with antibodies against glutamate decarboxylase (GAD), the gamma aminobutyric acid (GABA)-synthesizing enzyme, and somatostatin (SS). The immunoreactivity to these antibodies was detected by using biotinylated secondary antibodies and avidinated ferritin as an electron-dense marker. This electron microscopic double immunostaining procedure enabled us to demonstrate that immunoperoxidase-labeled ChAT-immunoreactive terminals established symmetric synaptic contacts on the ferritin-labeled GAD- and SS-immunoreactive hilar cells. In additional experiments at least some of the GAD- and SS-immunoreactive hilar neurons were further characterized as commissural neurons by retrograde filling with horseradish peroxidase (HRP) following an injection of the tracer into the contralateral hilus. From these triple labeling experiments, we concluded that at least some GABAergic and somatostatin-containing neurons in the hilar region, which are postsynaptic to cholinergic terminals, project to the contralateral hippocampus. Together with previous studies on the cholinergic innervation of the hippocampus and fascia dentata, our present results thus demonstrate that different types of hippocampal cells, including GABAergic and peptidergic commissural neurons in the hilar region, receive a cholinergic input.

GABAergic mechanisms of analgesia: an update.

Abstract: Both directly acting (GABAA and GABAB agonists) and indirectly acting GABAergic agents (GABA uptake inhibitors and GABA-transaminase inhibitors) produce analgesia in a variety of animal test systems. Analgesia produced by GABAA agonists is probably due to a supraspinal action, although spinal sites may also play a role. GABAA agonist analgesia is insensitive to naloxone, bicuculline, picrotoxin and haloperidol, but is blocked by atropine, scopolamine and yohimbine suggesting a critical role for central cholinergic and noradrenergic pathways in this action. The lack of blockade by the GABAA antagonist bicuculline is difficult to explain. Both bicuculline and picrotoxin have intrinsic analgesia actions which may not necessarily be mediated by GABA receptors. The GABAB agonist baclofen produces analgesia by actions at both spinal and supraspinal sites. Baclofen analgesia is insensitive to naloxone, bicuculline and picrotoxin, and blockade by cholinergic antagonists occurs only under limited conditions. Catecholamines are important mediators of baclofen analgesia because analgesia is potentiated by reserpine, alpha-methyl-p-tyrosine, phentolamine, ergotamine, haloperidol and chlorpromazine. A role for serotonergic mechanisms is less well defined. Methylxanthines, which produce a clonidine-sensitive increase in noradrenaline (NA) turnover, increase baclofen analgesia by a clonidine-sensitive mechanism. Both ascending and descending NA pathways are implicated in the action of baclofen because dorsal bundle lesions, intrathecal 6-hydroxydopamine and medullary A1 lesions markedly decrease baclofen analgesia. However, simultaneous depletion of NA in ascending and descending pathways by locus coeruleus lesions potentiates baclofen analgesia suggesting a functionally important interaction between the two aspects. Baclofen analgesia within the spinal cord may be mediated by a distinct baclofen receptor because GABA does not mimic the effect of baclofen and the rank order of potency both of close structural analogs of baclofen as well as antagonists differs for analgesia and GABAB systems. The spinal mechanism may involve an interaction with substance P (SP) because SP blocks baclofen analgesia, and desensitization to SP alters the spinal analgesic effect of baclofen. GABA uptake inhibitors produce analgesia which is similar to that produced by GABAA agonists because it is blocked by atropine, scopolamine and yohimbine. Analgesia produced by GABA-transaminase inhibitors is similar to that produced by GABAA agonists because it can be blocked by atropine, but it is potentiated by haloperidol while THIP analgesia is not.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of GABAergic neurons and axon terminals in the macaque striate cortex

Abstract: Antisera to glutamic acid decarboxylase (GAD) and γ-aminobutyric acid (GABA) have been used to characterize the morphology and distribution of presumed GABAergic neurons and axon terminals within the macaque striate cortex. Despite some differences in the relative sensitivity of these antisera for detecting cell bodies and terminals, the overall patterns of labeling appear quite similar. GABAergic axon terminals are particularly prominent in zones known to receive the bulk of the projections from the lateral geniculate nucleus; laminae 4C, 4A, and the cytochrome-rich patches of lamina 3. In lamina 4A, GABAergic terminals are distributed in a honeycomb pattern which appears to match closely the spatial pattern of geniculate terminations in this region. Quantitative analysis of axon terminals that contain flat vesicles and form symmetric synaptic contacts (FS terminals) in lamina 4Cβ and in lamina 5 suggest that the prominence of GAD and GABA axon terminal labeling in the geniculate recipient zones is due, at least in part, to the presence of larger GABAergic axon terminals in these regions. GABAergic cell bodies and their initial dendritic segments display morphological features characteristic of nonpyramidal neurons and are found in all layers of striate cortex. The density of GAD and GABA immunoreactive neurons is greatest in laminae 2–3A, 4A, and 4Cβ. The distribution of GABAergic neurons within lamina 3 does not appear to be correlated with the patchy distribution of cytochrome oxidase in this region; i.e., there is no significant difference in the density of GAD and GABA immunoreactive neurons in cytochrome-rich and cytochrome-poor regions of lamina 3. Counts of labeled and unlabeled neurons indicate that GABA immunoreactive neurons make up at least 15% of the neurons in striate cortex. Layer 1 is distinct from the other cortical layers by virtue of its high percentage (77–81%) of GABAergic neurons. Among the other layers, the proportion of GABAergic neurons varies from roughly 20% in laminae 2–3A to 12% in laminae 5 and 6. Finally, there are conspicuous laminar differences in the size and dendritic arrangement of GAD and GABA immunoreactive neurons. Lamina 4Cα and lamina 6 are distinguished from the other layers by the presence of populations of large GABAergic neurons, some of which have horizontally spreading dendritic processes. GABAergic neurons within the superficial layers are significantly smaller and the majority appear to have vertically oriented dendritic processes. These results provide support for the idea that GABAergic neurons make up a significant proportion of the neurons within the macaque striate cortex and that there are laminar differences in the number and the types of GABAergic neurons—differences that may be relevant for understanding the contributions of GABA-mediated inhibition to striate cortex function.

Immunocytochemistry of GABA in the brain and suboesophageal ganglion of Manduca sexta.

Abstract: We have used specific antisera against protein-conjugated gamma-aminobutyric acid (GABA) in immunocytochemical preparations to investigate the distribution of putatively GABAergic neurons in the brain and suboesophageal ganglion of the sphinx moth Manduca sexta. About 20,000 neurons per brain hemisphere exhibit GABA-immunoreactivity. Most of these are optic-lobe interneurons, especially morphologically centrifugal neurons of the lamina and tangential neurons that innervate the medulla or the lobula complex. Many GABA-immunoreactive neurons, among them giant fibers of the lobula plate, project into the median protocerebrum. Among prominent GABA-immunoreactive neurons of the median protocerebrum are about 150 putatively negative-feedback fibers of the mushroom body, innervating both the calyces and lobes, and a group of large, fan-shaped neurons of the lower division of the central body. Several commissures in the supra- and suboesophageal ganglion exhibit GABA-like immunoreactivity. In the suboesophageal ganglion, a group of contralaterally descending neurons shows GABA-like immunoreactivity. The frontal ganglion is innervated by immunoreactive processes from the tritocerebrum but does not contain GABA-immunoreactive somata. With few exceptions the brain nerves do not contain GABA-immunoreactive fibers.

The early development of neurons with GABA immunoreactivity in the CNS of Xenopus laevis embryos.

Abstract: We have used an antibody to glutaraldehyde fixation complexes of γ-amino butyric acid (GABA) to stain the developing central nervous system of Xenopus laevis embryos. Neuronal somata, growth cones, axons, and dendrites were found with GABA-like immunoreactivity. Transmission electron microscope (TEM) observations were made of axons and synapses. By observation of the earliest stages of differentiation of neurons, seven classes of putative GABAergic interneurons were discerned. (1) Ascending neurons are first stained in the hindbrain at stage 26 and later extend caudally in the spinal cord. They have ascending ipsilateral axons. (2) Midhindbrain reticulospinal neurons are first stained at stage 25 and develop as a compact group with descending ipsilateral and contralateral axons, (3) Vestibular complex commissural neurons are first stained at stage 29/30 in a dorsal position near the entry of the seventh and eighth cranial nerves. They have ventral commissural axons that descend contralaterally and their somata form a compact mass. (4) Rostral hindbrain commissural neurons are first stained at stage 33/34 just rostral to the entry of the trigeminal nerve. They each have a decussating projection. (5). Rostral midbrain neurons are first stained in the midbrain at stage 29/30 and are later associated with prominent dorsal and ventral commissures. (6) Optic tract and (7) rostral forebrain neurons are found in the forebrain associated with strongly stained axon tracts. The direction of axonal growth from its earliest stages was distinct for each class of hindbrain and spinal cord neuron.

gamma-Aminobutyric acid exerts a local inhibitory action on the axon terminal of bipolar cells: evidence for negative feedback from amacrine cells.

Abstract: It is well-established morphologically that bipolar cells, the second-order neurons in the vertebrate retina, make reciprocal synapses with amacrine cells in the inner plexiform layer. However, neither the property nor the physiological function of the feedback synapse is understood. Autoradiographic and immunohistochemical studies suggest the presence of gamma-aminobutyric acid (GABA)-ergic amacrine cells, and therefore the bipolar cells are thought to receive GABAergic inputs from amacrine cells. This possibility was investigated in the present study, in which we used solitary bipolar cells dissociated from the goldfish retina enzymatically. Dissociated solitary bipolar cells showed a large variety in morphology. In the present study, we selected the bipolar cells with a huge bulbous axon terminal. Bipolar cells of this subtype were identical in morphology to the on-center cells with rod-dominant inputs as revealed in earlier studies by intracellular staining. Membrane currents were measured under voltage clamp with a patch pipette in the whole cell configuration. In some experiments, GABA-sensitive membrane was excised as an outside-out patch from the axon terminal bulb of solitary bipolar cells. All cells of this type responded to GABA. The highest sensitivity was located at the axon terminal. The minimal effective dose was on the order of 10(-7) M. GABA increased the chloride conductance and evoked a membrane hyperpolarization. Partial desensitization was observed during the application of GABA. The bipolar cells had GABA type A receptors. These results are consistent with the idea that the rod-dominant on-center bipolar cells receive negative feedback inputs from GABAergic amacrine cells.

Development of the nervous system of the pluteus larva of Strongylocentrotus droebachiensis

Abstract: Development of the nervous system of the pluteus larva of Strongylocentrotus droebachiensis was investigated using indirect immunofluorescence with antibodies against dopamine, GABA, and serotonin, and glyoxylic acid-induced fluorescence of catecholamines. Serotonergic cells first appear in full gastrulae; dopaminergic and GABAergic cells are present in early four-arm plutei. The number of neurons and the complexity of the nervous system increases through development of the pluteus. In the pluteus the dopaminergic component of the nervous system includes a ganglion in the lower lip of the mouth and a pair of ganglia at the base of the post-oral arms which extend axons along the base of the circumoral ciliary band. The distribution of cells visualized by glyoxylic acid-induced fluorescence is similar to that of dopaminergic cells. GABAergic neurons occur in the upper lip and in the wall of the esophagus. Serotonergic neurons are present in the lower lip; the pre-oral hood contains an apical ganglion which extends axons along the base of the epidermis overlying the blastocoel. The dopaminergic and GABAergic components of the nervous system are associated with effectors involved in feeding and swimming. The serotonergic component is not associated with any apparent effectors but may have a role in metamorphosis.

Synaptic organization of GABAergic neurons in the mouse SmI cortex

Abstract: Immunocytochemical methods were used to examine GABAergic neurons in the barrel region of the mouse primary somatosensory cortex. GABAergic neurons occur in all layers of the barrel cortex but are more concentrated in the upper portion of layers II/III and in layers IV and VI. Nine cells in layer IV were examined with the electron microscope, and portions of their dendrites were reconstructed from serial thin sections. These cells are of the nonspiny, multipolar or bitufted varieties, and some of them have beaded dendrites. The labeled cell bodies and their reconstructed dendrites were postsynaptic at asymmetrical synapses with thalamocortical axon terminals labeled by lesion-induced degeneration and with unlabeled axon terminals. Each cell also received symmetrical synapses from GABAergic axon terminals and from unlabeled axon terminals. Our results indicate that GABAergic cell bodies and processes receive synapses from thalamocortical axon terminals but that different cells display marked differences in the proportion of thalamocortical and other synapses they receive. These results indicate that GABAergic cells form a heterogeneous population with respect to their morphologies and patterns of synaptic inputs. The synaptic sequences revealed here for GABAergic neurons represent an anatomical substrate for various inhibitory processes known to occur within the cerebral cortex.

An electron microscopic study of GABAergic neurons and terminals in the central nucleus of the inferior colliculus of the rat.

Abstract: Neurons and terminals in the ventral lateral portion of the central nucleus of the inferior colliculus (ICCN) of the rat were labelled immunocytochemically with antisera to GABA or to its synthesizing enzyme, glutamic acid decarboxylase. Four types of GABAergic neuron are described: small, medium-sized and large multipolar neurons, as well as medium-sized bipolar neurons. All sizes of GABAergic multipolar neurons are characterized by highly infolded nuclei, many mitochondria and both asymmetric and symmetric axosomatic synapses. A dense plexus of terminals occurs on the proximal dendrites of GABAergic neurons, and most of these terminals form asymmetric axodendritic contacts. Small GABAergic neurons (diameter less than 15 microns) are multipolar, and have a large nucleus to cytoplasm ratio, prominent nucleoli and usually two to five axosomatic synapses per thin section, with the majority of these contacts being symmetric. Medium-sized GABAergic neurons (15-25 microns in diameter) display both multipolar and fusiform shaped somata, have a more abundant cytoplasm than the small neurons and show about ten axosomatic contacts per thin section. Large GABAergic neurons (diameters greater than 25 microns) have eccentrically located, highly infolded nuclei, abundant cytoplasm and a denser plexus of terminals that form axosomatic synapses than the other cell types. These results indicate that four of the six major cell types in the ICCN are probably GABAergic inhibitory neurons. The axon initial segments of GABAergic neurons in the ICCN all have similar features in that they are contacted by only one or two terminals that form symmetric synapses on their proximal portions and are invested by a glial sheath from 3 to 20 microns from the cell body. Many immunoreactive myelinated axons (approximately 0.5 micron in diameter) are observed and some terminals that arise from these axons form synapses with small neuronal somata. Both these and other labelled terminals are shown to form symmetric synapses. These data suggest a complex circuitry for the GABAergic neurons within the ICCN.

Fluorescence-activated cell sorting of embryonic mouse and rat motoneurons and their long-term survival in vitro

Abstract: Motoneurons from embryonic mice and rats were labeled with retrogradely transported succinyl wheat germ agglutinin (WGA)-fluorescein isothiocyanate (FITC). After dissociation of the spinal cord, fluorescent motoneurons were isolated by flow cytometry. Sorted motoneurons were maintained for as long as 6 weeks in vitro on monolayers of astrocytes in muscle-conditioned medium. Immunocytochemical staining of the cultures for various neuronal antigens suggested that sorted motoneurons are receptive to GABAergic and glycinergic, as well as cholinergic, innervation. Many of the sorted cells were also labeled intracellularly with antibodies to choline acetyltransferase (ChAT) and GABA.

Primary Cultures of Gabaergic and Glutamatergic Neurons as Model Systems to Study Neurotransmitter Functions I. Differentiated Cells

Abstract: The complexity of the central nervous system (CNS) has necessitated the development of different methodologies, e.g., microdissection, separation by gradient centrifugation, and cell culturing, to study the characteristics of individual cell types. In the present review, we discuss results obtained using one of these preparations, i.e., neurons in primary cultures. By definition such cultures are obtained directly from the living animal, often at an immature stage, and maintained in vitro for at least 24 hours (Fedoroff, 1977). One advantage of the tissue culture system is that it is possible to obtain highly enriched populations of specific cell types. Since the cells are obtained from immature brain tissue, it is, however, essential to ensure that an appropriate development has occurred during the culturing period. Such alterations during development in vitro will be discussed in chapter 3. In this chapter, we discuss characteristics of neurons that have already differentiated during a prolonged culturing period (≃ 2 weeks). The selected characteristics are related to transmitter function, i.e., release, high-affinity uptake, biosynthesis, and receptor interactions of the neurotransmitters γ-aminobutyric acid (GABA) and glutamate. For this purpose, two different culture preparations, i.e., cerebral cortical interneurons and cerebellar granule cells, have been used. From in vivo studies it is known that the cortical interneurons use GABA (Ribak, 1978) and the cerebellar granule cells glutamate (Young et al., 1974; Hudson et al., 1976; Stone, 1979) as their transmitter.

Immunocytochemical and pharmacological evidence for GABAergic spiking local interneurons in the locust

Abstract: In the locust thoracic nervous system, spiking local interneurons within a ventral midline population are stained by a polyclonal antibody raised against GABA. Their cell bodies, their primary neurites in ventral commissure II, and their prominent neurites in the perpendicular tract linking ventral and dorsal fields of fine branches are all stained. Individual interneurons in this population were labeled with Lucifer yellow after their receptive fields had been determined physiologically. Alternate sections were stained with the antibody. Some, but not all, of the spiking local interneurons labeled with Lucifer yellow are also stained with the antibody. Apart from having somata that lie more posteriorly within the midline population, the antibody-stained interneurons cannot be distinguished on morphological or physiological grounds from those that are unstained. The way in which this cytochemical heterogeneity within an otherwise homogenous population might arise during development is discussed. A second group of spiking local interneurons with similar sensory input to that of the ventral midline population, but with cell bodies in the anterior lateral region of the ganglion and primary neurites in ventral commissure I, are not stained. Interneurons in the midline group receive direct inputs from sensory neurons and some directly inhibit particular leg motor neurons that mediate interjoint and tactile reflexes. Picrotoxin reversibly blocks the inhibition of the motor neurons and therefore abolishes these reflexes. Immunocytochemical and pharmacological experiments thus suggest that inhibition by some spiking local interneurons may be mediated by GABA.

Hippocampus of the seizure‐sensitive gerbil is a specific site for anatomical changes in the GABAergic system

Abstract: The brains of seizure-sensitive (SS) and seizure-resistant (SR) gerbils were studied with an immunocytochemical method to localize glutamic acid decarboxylase (GAD) to determine whether a defect existed in the inhibitory GABAergic system similar to that which has been reported in animal models of focal epilepsy in which GABAergic cell bodies and terminals are decreased in number. A major difference between the two strains of gerbils was found in the number of GABAergic neurons in the hippocampal formation. Specifically, a paradoxical increase occurred in the number of glutamate decarboxylase (GAD)-immunoreactive neurons: there were approximately 65% more GABAergic cells within the dentate gyrus and the CA3 region of the hippocampus in the SS gerbils. Furthermore, the density of GAD-immunoreactive puncta, the light microscopic correlates of synaptic boutons, was greater in the SS animals. Other histological methods were used to determine if the difference between SS and SR gerbils was specific for the GABAergic system. Nissl-stained preparations showed that the number of granule cells in the dentate gyrus was 20% greater in SS gerbils than in SR gerbils. An examination of some hippocampal afferents, efferents, and intrinsic connections with acetylcholinesterase histochemistry and the Timm's stain for heavy metals demonstrated no differences between the two strains. In addition, Golgi-stained preparations of the dentate gyrus indicated that the morphology of basket cells did not differ between the two strains nor between the gerbil and the rat. Several brain regions in addition to the hippocampus were studied to determine whether or not the increased number of GAD-immunoreactive neurons was specific for the hippocampal formation. These regions included the substantia nigra, motor cortex, and nucleus reticularis thalami and were selected because they contain large populations of GABAergic neurons and have been implicated in seizure activity. No differences between the two strains were detected in any of these regions. Therefore, a major morphological difference between the brains of SS and SR gerbils exists in the hippocampal formation of SS gerbils in which an increase occurs in the number of GABAergic neurons and granule cells. If these additional inhibitory neurons act mainly to inhibit other inhibitory neurons, the net effect would be increased disinhibition of the principal excitatory neurons of the hippocampal formation. This could lead to seizure activity within the hippocampal formation and at distant sites through multiple synaptic connections.