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G Buzsaki

Publications and source records attributed to G Buzsaki.

16 recordsLinked to original sources
PubMed1999

The entorhino-septo-supramammillary nucleus connection in the rat: morphological basis of a feedback mechanism regulating hippocampal theta rhythm.

Recent electrophysiological observations suggest that, in addition to the medial septal area pacemaker system, several alternative or additional mechanisms are involved in the generation/regulation of hippocampal theta activity. Discharging neurons phase-locked to hippocampal theta waves have been observed in the dorsal raphe, nucleus reticularis pontis oralis and especially in the supramammillary region of rats. Since these areas are reciprocally interconnected with the hippocampal formation, including the entorhinal cortex, it would aid our understanding of limbic function to elucidate the location and neurochemical content of the entorhino-septal and septo-supramammillary projection neurons, as well as that of their postsynaptic targets. Light and electron microscopic immunostaining for calretinin, in combination with antero- and retrograde tracer techniques, postembedding immunostaining for GABA and the transmitter specific [3H]D-aspartate retrograde radiolabeling, as well as a co-localization experiment for calretinin and glutamate decarboxylase in rat supramammillary and septal neurons, demonstrated that: (i) a large population of entorhinal cells that forms asymmetric synaptic contacts on calretinin-containing neurons located at the border between the medial and lateral septal areas contains calretinin and are aspartate/glutamatergic; (ii) the overwhelming majority of calretinin-immunoreactive cells located at the border between the lateral and medial septal area are GABAergic; (iii) these neurons can be retrogradely labeled from the supramammillary area; (iv) anterogradely labeled axons originating in the border between the medial and lateral septum are GABAergic and (v) terminate on supramammillary area non-GABAergic, calretinin-containing neurons, which are known to project to the septal complex and hippocampus. These observations indicate that a large population of cells participating in the hippocampal feedback regulation of theta regulation/generation contain the same calcium-binding protein. Furthermore, entorhinal excitatory transmitter-containing neurons can depress the activity of supramammillary theta generating/regulating cells via septal inhibitory neurons.

Animals↗
PubMed1998

Dendritic properties of hippocampal CA1 pyramidal neurons in the rat: intracellular staining in vivo and in vitro.

Dendritic morphology and passive cable properties determine many aspects of synaptic integration in complex neurons, together with voltage-dependent membrane conductances. We investigated dendritic properties of CA1 pyramidal neurons intracellularly labeled during in vivo and in vitro physiologic recordings, by using similar intracellular staining and three-dimensional reconstruction techniques. Total dendritic length of the in vivo neurons was similar to that of the in vitro cells. After correction for shrinkage, cell extent in three-dimensional representation was not different between the two groups. Both in vivo and in vitro neurons demonstrated a variable degree of symmetry, with some neurons showing more cylindrical symmetry around the main apical axis, whereas other neurons were more elliptical, with the variation likely due to preparation and preservation conditions. Branch order analysis revealed no difference in the number of branch orders or dendritic complexity. Passive conduction of dendritic signals to the soma in these neurons shows considerable attenuation, particularly with higher frequency signals (such as synaptic potentials compared with steady-state signals), despite a relatively short electrotonic length. Essential aspects of morphometric appearance and complex dendritic integration critical to CA1 pyramidal cell functioning are preserved across neurons defined from the two different hippocampal preparations used in this study.

Animals↗
PubMed1998

Induction of calcitonin gene-related peptide-like immunoreactivity in hippocampal neurons following ischemia: a putative regional modulator of the CNS injury/immune response.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and immune cell modulator. In two studies within the hippocampal formation (HF), CGRP-like immunoreactivity (CGRP-LI) was increased in the inner molecular layer of the dentate gyrus after adrenalectomy and in mossy cells after colchicine-induced destruction of granule neurons. Given the increase in CGRP-LI following damage to the granule cell region of the HF, we investigated another trauma model, ischemia, that targeted different areas of the HF, CA1 region, and subiculum to ascertain the regional expression of this peptide after insult. Following ischemia, light microscopic evaluation showed CGRP-LI in basket cell-like neuronal perikarya within the dorsal subiculum and CA1 region of the hippocampus and in varicose fibers within the CA2 region of the hippocampus. Control rats rarely expressed CGRP-LI within neurons in these regions. In ischemic brains, double-labeled immunocytochemistry with antibodies to various neural markers demonstrated co-localization of CGRP-LI primarily within surviving subicular and CA1 cells resembling interneurons containing parvalbumin-LI or calbindin-LI. Electron microscopic analysis of the CA1 region from ischemic brains showed that CGRP-LI was contained in terminals with numerous small synaptic vesicles that formed symmetric synapses with perikarya and large dendrites of pyramidal cells, some of which were degenerating. Collectively, the data from this study and our previous study indicate that damage induces CGRP-LI expression in interneurons and nonprincipal cells in the area of damage, and we hypothesize that CGRP expression in surviving neurons within damage-related regions of the hippocampus is likely to be an important, and possibly a protective, component of the response of the nervous system to injury.

Adrenalectomy↗
PubMed1996

Entorhinal cortical innervation of parvalbumin-containing neurons (Basket and Chandelier cells) in the rat Ammon's horn.

Physiological data suggest that in the CA1-CA3 hippocampal areas of rats, entorhinal cortical efferents directly influence the activity of interneurons, in addition to pyramidal cells. To verify this hypothesis, the following experiments were performed: 1) light microscopic double-immunostaining for parvalbumin and the anterograde tracer Phaseolus vulgaris-leucoagglutinin injected into the entorhinal cortex; 2) light and electron microscopic analysis of cleaved spectrin-immunostained (i.e., degenerating axons and boutons) hippocampal sections following entorhinal cortex lesion; and 3) an electron microscopic study of parvalbumin-immunostained hippocampal sections after entorhinal cortex lesion. The results demonstrate that in the stratum lacunosum-moleculare of the CA1 and CA3 regions, entorhinal cortical axons form asymmetric synaptic contacts on parvalbumin-containing dendritic shafts. In the stratum lacunosum-moleculare, parvalbumin-immunoreactive dendrites represent processes of GABAergic, inhibitory basket and chandelier cells; these interneurons innervate the perisomatic area and axon initial segments of pyramidal cells, respectively. A feed-forward activation of these neurons by the entorhinal input may explain the strong, short-latency inhibition of pyramidal cells.

Animals↗
PubMed1995

Morphometric and electrical properties of reconstructed hippocampal CA3 neurons recorded in vivo.

CA3 pyramidal neurons were stained with biocytin during intracellular recording in rat hippocampus in vivo and reconstructed using a computer-based system. The in vivo CA3 neurons were characterized primarily according to their proximity to the hilus and secondarily with respect to the septotemporal location. Neurons measured in CA3a (n = 4), in CA3b (n = 4), and in posterior/ventral locations (n = 3) had the greatest dendritic lengths (19.8, 19.1, and 26.8 mm on average, respectively). Cells closer to the hilus showed much shorter dendritic lengths, averaging 10.4 mm for CA3c neurons (n = 4) and 11.6 mm for zone 3 neurons (n = 2). Half of the cells showed more than one major apical dendrite, and dendritic trees were highly variable even within CA3 subregions. The mean electronic length for these cell groups averaged between 0.30 lambda (CA3c) and 0.45 lambda (posterior/ventral), assuming a constant specific-membrane resistivity of 60 K omega-cm2. These CA3 neurons form a database of reconstructed neurons for further morphometric and electrical modelling studies. The large degree of variability between individual CA3 neurons indicates that both dendritic and electrical properties should be specifically calculated for each cell rather than assuming a "typical" morphology.

Animals↗
PubMed1995

Epileptic seizures caused by inactivation of a novel gene, jerky, related to centromere binding protein-B in transgenic mice.

Epidemiological data and genetic studies indicate that certain forms of human epilepsy are inherited. Based on the similarity between the human and mouse genomes, mouse models of epilepsy could facilitate the discovery of genes associated with epilepsy syndromes. Here, we report an insertional murine mutation that inactivates a novel gene and results in whole body jerks, generalized clonic seizures, and epileptic brain activity in transgenic mice. The gene, named jerky, encodes a putative 41.7 kD protein displaying homology to a number of nuclear regulatory proteins, suggesting that perhaps the jerky protein is able to bind DNA.

Amino Acid Sequence↗
PubMed1992

Delayed degeneration of the optic tract and neurons in the superior colliculus after forebrain ischemia.

Neuronal damage induced by 15-min forebrain ischemia was investigated in adult rats 1-5 days (short-term group) and 1-5 months (long-term group) after the initial ischemic attack. In addition to the vulnerable areas reported previously, we observed that the optic tract was also very susceptible. Degeneration of the optic tract and subsequent transsynaptic cell death in the superior colliculus developed slowly and was observed only in the long-term group. The delayed, progressive neuronal damage in this sensory system may serve as a suitable model to investigate the mechanisms of long-term changes in the injured brain.

Animals↗
PubMed1990

Nucleus basalis lesions fail to induce senile plaques in the rat.

Fourteen months after receiving bilateral ibotenic acid lesions of the nucleus basalis magnocellaris (NBM), male rats demonstrated impairment in spatial learning in a water maze task, increased incidence of high voltage spindles, and significant depletion of cortical choline acetyltransferase (ChAT) activity. Histological evaluation revealed decreased acetylcholinesterase (AChE) staining but no plaque-like structures in the cortex.

Acetylcholinesterase↗
PubMed1990

Hippocampal cell death following ischemia: effects of brain temperature and anesthesia.

The effect of brain temperature and anesthesia on ischemic neuronal damage was studied in the hippocampal formation using the four vessel occlusion model in awake and anesthetized rats. Neuronal damage was assessed by immunocytochemistry and silver impregnation of tissue sections. The degree of ischemia was monitored by recording spontaneous and evoked electrical activity from the hippocampus and dentate gyrus in all animals. In addition, the hippocampal temperature and oxygen tension were also recorded using a chamber-type thin-film microelectrode in the anesthetized animals. Fifteen minutes ischemia in the awake animals caused greater neuronal damage and mortality of animals than 30 min ischemia in anesthetized rats. The temperature of the brain was found to drop by 4-6 degrees C during complete forebrain ischemia in the latter group. Neuronal damage was observed infrequently in the hippocampus of these animals. When the brain temperature was kept constant at the preischemic level during 30 min occlusion, all animals died within a day, while after 15 min occlusion the majority showed an almost complete degeneration of CA1 pyramidal cells and hilar somatostatin immunoreactive neurons. Following 15 min ischemia, the awake animals showed a similar cell loss in the CA1 region and the hilus. It is concluded that, in the anesthetized animals prepared for acute recording, the decreased temperature of the brain during ischemia is a major factor in protecting neurons from damage, but that Equithesin anesthesia also has a significant protective effect. Consistent ischemic degeneration occurs in awake animals by four vessel occlusion, if the brain temperature is controlled and the completeness of ischemia is monitored by recording spontaneous and evoked electrical activity with chronic electrodes.

Anesthetics↗
PubMed1990

Nerve growth factor infusions combined with fetal hippocampal grafts enhance reconstruction of the lesioned septohippocampal projection.

A combination of intracerebral grafting and intraventricular infusion of nerve growth factor was used to attempt to reconstruct the cholinergic component of the septohippocampal pathway following fimbria-fornix lesions in the rat. Four groups were tested: lesion only, lesion plus fetal hippocampal graft, lesion plus nerve growth factor, and lesion plus graft plus nerve growth factor. Choline acetyltransferase immunoreactivity, acetylcholinesterase fiber staining and behavior-dependent theta activity on electroencephalogram were used to assess the extent of pathway reconstruction. Nerve growth factor was infused for the first two weeks following the fimbria-fornix lesion, while electrophysiological measurements and histological analysis were conducted six to eight months later. The lesion plus graft plus nerve growth factor infusion group had long-term savings of choline acetyltransferase-immunoreactive cells as compared to the lesion only or lesion plus graft groups. In addition the lesion plus graft plus nerve growth factor infusion group had more extensive reinnervation of the hippocampus compared to all other groups. Behavioral-dependent theta activity on electroencephalogram was observed in some animals of both lesion plus graft and lesion plus graft plus nerve growth factor infusion groups, but not in other groups; however, unlike intact animals, the restored theta could be blocked completely by scopalamine. These results demonstrate that a combination of short-term intraventricular nerve growth factor infusion and fetal hippocampal grafts enhances reconstruction of the damaged septohippocampal circuit.

Animals↗
PubMed1988

Neocortical and hippocampal electrical activity following decapitation in the rat.

It has been debated whether or not decapitation of conscious animals is a humane procedure. This problem may be clarified on the basis of recent research that has indicated that neocortical low voltage fast activity (LVFA) and hippocampal rhythmical slow activity (RSA) can result from activity in either the cholinergic corticipetal projections from the basal forebrain or the serotonergic corticipetal projections from the brainstem. These inputs appear to produce, respectively, atropine-sensitive LVFA and RSA and atropine-resistant LVFA and RSA. In waking animals, atropine-resistant LVFA and RSA occur only in close correlation with motor activities such as spontaneous changes in posture, walking or struggling (Type 1 behavior). Painful stimuli readily elicit both Type 1 behavior and LVFA and RSA in atropine-treated rats. Atropine-sensitive LVFA and RSA may occur in anesthetized as well as in conscious animals, but atropine-resistant LVFA and RSA are generally absent during anesthesia. In the experiments reported here, rats were decapitated: (1) in the normal waking state; (2) after pretreatment with atropine or scopolamine; or (3) following induction of anesthesia with ethyl ether. Clear hippocampal RSA and neocortical LVFA were observed in conditions 1 and 3 but not in condition 2. It is concluded: (A) that atropine-sensitive LVFA and RSA are not good indices of conscious perception of pain since these waveforms occur during anesthesia as well as in the waking state; and (B) that the cerebral reaction to decapitation does not resemble the usual cerebral reaction to painful stimuli. This is consistent with the view that decapitation is not inhumane.

Animals↗
PubMed1988

Nucleus basalis and thalamic control of neocortical activity in the freely moving rat.

EEG and single-unit techniques have been used to study the EEG correlates of cellular firing in the neocortex, n. reticularis (RT) and "specific" thalamic nuclei, and the cholinergic forebrain area (nucleus basalis, NB). Neuronal firing was related to the ongoing behavior of the rat. In addition, using a 16-channel neocortical recording/mapping system, we studied the effects of ibotenic acid lesion of NB, RT, and other thalamic nuclei on the patterns and spatial distribution of neocortical electrical activity. The majority of neurons in neocortex, NB, and RT increased their firing rates during walking, as compared to during immobility, with concurrent decrease of delta power in the neocortical EEG. During immobility, high-voltage spindles (HVS; greater than 1 mV) were occasionally recorded from the neocortex. Depth profiles of HVS and slow delta waves were different in the neocortex. Neocortical cells decreased their discharge frequency during the positive portion of delta waves recorded in layers V and VI. All cells in the neocortex and specific thalamic nuclei fired rhythmically and phase-locked to the spike component of HVS. RT neurons showed an opposite phase relationship and fired mainly during the wave component of HVS. Half of the NB neurons also showed phasic modulation with HVS. Circumscribed lesion of RT and extensive damage of other thalamic regions, including the intralaminar nuclei, suppressed HVS but had no effect on the neocortical EEG correlates of behavior. In sharp contrast, damage to the NB resulted in a dramatic increase of slow delta waves on the side of the lesion, mimicking the effect of scopolamine administration. We suggest that the NB plays a key role in neocortical arousal by directly activating the neocortex and by suppressing the rhythm generation in the RT-thalamocortical circuitry. We further suggest that the NB system may serve as a structural basis for the concept of the generalized ascending activation of Moruzzi and Magoun (1949).

Animals↗
PubMedDate not supplied

Morphologic alterations of choline acetyltransferase-positive neurons in the basal forebrain of aged behaviorally characterized Fisher 344 rats.

We examined Fisher 344 female rats aged 6, 27, and 33 months old. Prior to sacrifice and morphometric analyses of forebrain cholinergic neurons all rats underwent behavioral characterization in a spatial learning task using the Morris water maze. Performance on the spatial task permitted subsequent grouping of the 27- and 33-month-old animals into impaired or nonimpaired groups. Importantly, the percentage of animals that displayed spatial impairments increased sharply with advancing age. Quantitative assessment of the size and density of choline acetyltransferase (ChAT)-positive neurons throughout the basal forebrain revealed a significant enlargement of forebrain cholinergic neurons within 27-month-old nonimpaired rats compared to 6-month-old rats and 27- and 33-month-old impaired animals. This increase in size was most noted in the medial septum and nucleus of the diagonal band. Significant decreases in the density of ChAT-positive neurons was observed only in the nucleus of the diagonal band of 27-month-old impaired rats compared to 6-month-old controls. Although the significance of enlarged forebrain cholinergic neurons is unclear, we discuss the possibility that within aged rodents neuronal swelling is an active event and represents an early manifestation of the aging process and may constitute a restorative and/or compensatory event in that these rats are relatively asymptomatic with respect to their behavioral deficits. In addition, we discuss in some detail various technical and life effect issues which may vary the outcome of investigations of aged rodents.

Aging↗
PubMedDate not supplied

Experimental approaches to age-related cognitive impairments.

Rats exhibit morphological, biochemical, and metabolic changes in their brains, as well as cognitive deficits, with aging. Aged rats were found to be significantly impaired compared to young rats in a water maze task and test of motor coordination, and show reduced locomotor activity and exploration. Although aged rats did exhibit deficits as a group, not all aged rats were impaired. Additionally, the subgroup that was impaired on one task was not necessarily the subgroup that was impaired on another task. The cholinergic projection neurons in the basal forebrain region were significantly atrophied in the aged rodent. The degree of atrophy was highly correlated with the cognitive impairment exhibited on the Morris water maze task. Swollen choline acetyltransferase (ChAT)-positive "plaque-like" structures were observed in the neocortex of the aged but not the young rats. Declines in cholinergic activity in the brain has also been observed during aging. Biochemical measurements of ChAT in the basal forebrain region of aged rats revealed small but consistent decreases in ChAT activity compared to young rats. General metabolic activity, measured by the 2-deoxyglucose method, was also decreased in the hippocampal CA1 and CA3 fields, the dentate gyrus, the medial septal-diagonal band area, and the prefrontal cortex of aged rats. There was a significant correlation between the decrease in glucose utilization and deficits on the Morris water maze. Most aged rats exhibit pathological EEG patterns as reflected by frequent long-duration high voltage neocortical spindles (HVS) during immobility. Bilateral lesions of the nucleus basalis and scopolamine treatment increased the incidence of HVS, thereby mimicking changes in the aged brain. We attempted to ameliorate the cognitive deficits observed in subgroups or impaired rats by either: (1) implanting fetal cells of basal forebrain origin into the hippocampus, or (2) infusing nerve growth factor (NGF) chronically into the lateral ventricle. The grafts appeared to facilitate an improvement in the ability of the impaired aged rats to perform in the Morris water maze. This improved performance was reversed by injections of atropine at doses that did not affect the behavior of young animals that performed well in the same task. These results suggest that enhancement of the cholinergic system could have an effect on the performance of the impaired aged animals. The study of the effects of infusions of NGF clearly demonstrate that the ability of impaired aged rats to remember what they had previously learned was increased after NGF treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗