Possible physiological role of the perforant path-CA1 projection.
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Biomedical subjects
A Bragin
Publications and source records attributed to A Bragin.
GABAergic inhibition of granule cells and hilar neuronal synchrony following ischemia-induced hilar neuronal loss.
In the dentate gyrus, granule cells are ischemia-resistant, but at least five types of predominantly spiny hilar neurons are extremely vulnerable to ischemia. Many of the ischemia-sensitive subtypes of hilar neurons appear to be involved in: (i) the regulation of GABAergic inhibition in the dentate gyrus, and (ii) the generation of hilar neuronal synchrony. The present study examined functional consequences of ischemia-induced hilar neuronal loss on GABAergic inhibition of granule cells and hilar neuronal synchrony. Transient (15 min) forebrain ischemia was induced by a modification of the four-vessel-occlusion method producing a substantial hilar neuronal loss as demonstrated by the Gallyas silver stain method. Three months later, we have examined spontaneous and stimulus-evoked inhibitory postsynaptic currents mediated by both GABA(A) and GABA(B) receptors, and inhibitory bursts induced by 4-aminopyridine (50 microM) using whole-cell recordings in coronal brain slices maintained at 34-36 degree C in the presence of excitatory amino acid receptor blockers. Spontaneous dentate spikes reflecting hilar neuronal synchrony and synaptic responses evoked by perforant path stimulation were also recorded in vivo to assess synchrony and inhibition in the dentate gyrus. In spite of significant damage to several types of hilar neurons, there were no marked differences in the conductance, kinetics, and 4-aminopyridine-induced burst frequencies of synaptic GABA(A) and GABA(B) responses in granule cells. Furthermore, both paired-pulse inhibition and dentate spikes appeared to be normal in vivo. We conclude that there appears to be little impairment of GABAergic inhibition of granule cells or of hilar neuronal synchrony three months following a massive ischemic damage to spiny hilar neurons.
4-Aminopyridine↗
Dentate EEG spikes and associated interneuronal population bursts in the hippocampal hilar region of the rat.
1. This paper describes two novel population patterns in the dentate gyrus of the awake rat, termed type 1 and type 2 dentate spikes (DS1, DS2). Their cellular generation and spatial distribution were examined by simultaneous recording of field potentials and unit activity using multiple-site silicon probes and wire electrode arrays. 2. Dentate spikes were large amplitude (2-4 mV), short duration (< 30 ms) field potentials that occurred sparsely during behavioral immobility and slow-wave sleep. Current-source density analysis revealed large sinks in the outer (DS1) and middle (DS2) thirds of the dentate molecular layer, respectively. DS1 and DS2 had similar longitudinal, lateral, and interhemispheric synchrony. 3. Dentate spikes invariably were coupled to synchronous population bursts of putative hilar interneurons. CA3 pyramidal cells, on the other hand were suppressed during dentate spikes. 4. After bilateral removal of the entorhinal cortex, dentate spikes disappeared, whereas sharp wave-associated bursts, reflecting synchronous discharge of the CA3-CA1 network, increased several fold. 5. These physiological characteristics of the dentate spikes suggest that they are triggered by a population burst of layer II stellate cells of the lateral (DS1) and medial (DS2) entorhinal cortex. 6. We suggest that dentate spike-associated synchronized bursts of hilar-region interneurons provide a suppressive effect on the excitability of the CA3-CA1 network in the intact brain.
Animals↗
Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms.
Sharp wave bursts, induced by a cooperative discharge of CA3 pyramidal cells, are the most synchronous physiological pattern in the hippocampus. In conjunction with sharp wave bursts, CA1 pyramidal cells display a high-frequency (200 Hz) network oscillation (ripple). In the present study extracellular field and unit activity was recorded simultaneously from 16 closely spaces sites in the awake rat and the intracellular activity of CA1 pyramidal cells during the network oscillation was studied under anesthesia. Current source density analysis of the high-frequency oscillation revealed circumscribed sinks and sources in the vicinity of the pyramidal layer. Single pyramidal cells discharged at a low frequency but were phase locked to the negative peak of the locally derived field oscillation. Approximately 10% of the simultaneously recorded pyramidal cells fired during a given oscillatory event. Putative interneurons increased their discharge rates during the field ripples severalfold and often maintained a 200 Hz frequency during the oscillatory event. Under urethane and ketamine anesthesia the frequency of ripples was slower (100-120 Hz) than in the awake rat (180-200 Hz). Halothane anesthesia prevented the occurrence of high-frequency field oscillations in the CA1 region. Both the amplitude (1-4 mV) and phase of the intracellular ripple, but not its frequency, were voltage dependent. The amplitude of intracellular ripple was smallest between -70 and -80 mV. The phase of intracellular oscillation relative to the extracellular ripple reversed when the membrane was hyperpolarized more than -80 mV. A histologically verified CA1 basket cell increased its firing rate during the network oscillation and discharged at the frequency of the extracellular ripple. These findings indicate that the intracellularly recorded fast oscillatory rhythm is not solely dependent on membrane currents intrinsic to the CA1 pyramidal cells but it is a network driven phenomenon dependent upon the participation of inhibitory interneurons. We hypothesize that fast field oscillation (200 Hz) in the CA1 region reflects summed IPSPs in pyramidal cells as a result of high-frequency barrage of interneurons. The sharp wave associated synchronous discharge of pyramidal cells in the millisecond range can exert a powerful influence on retrohippocampal targets and may facilitate the transfer of transiently stored memory traces from the hippocampus to the entorhinal cortex.
Anesthesia↗
Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat.
The cellular generation and spatial distribution of gamma frequency (40-100 Hz) activity was examined in the hippocampus of the awake rat. Field potentials and unit activity were recorded by multiple site silicon probes (5- and 16-site shanks) and wire electrode arrays. Gamma waves were highly coherent along the long axis of the dentate hilus, but average coherence decreased rapidly in the CA3 and CA1 directions. Analysis of short epochs revealed large fluctuations in coherence values between the dentate and CA1 gamma waves. Current source density analysis revealed large sinks and sources in the dentate gyrus with spatial distribution similar to the dipoles evoked by stimulation of the perforant path. The frequency changes of gamma and theta waves positively correlated (40-100 Hz and 5-10 Hz, respectively). Putative interneurons in the dentate gyrus discharged at gamma frequency and were phase-locked to the ascending part of the gamma waves recorded from the hilus. Following bilateral lesion of the entorhinal cortex the power and frequency of hilar gamma activity significantly decreased or disappeared. Instead, a large amplitude but slower gamma pattern (25-50 Hz) emerged in the CA3-CA1 network. We suggest that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus. We also hypothesize that under physiological conditions the hilar gamma oscillation may be entrained by the entorhinal rhythm and that gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.
Animals↗
Number of GABA-immunopositive and GABA-immunonegative neurons in various types of neocortical transplants.
Quantitative investigation of GABA-immunopositive and GABA-immunonegative neurons was performed in grafts of embryonic tissue of somatosensory cortex, (1) injected intraparenchymally into the barrel field of adult rats (n = 5); (2) placed in an acute cavity in the same area (n = 9); or (3) implanted into the anterior eye chamber (n = 5). Analysis of initial embryonic tissue at the age of grafting (E17) demonstrated high numerical density of neurons both GABA-positive and other. Six months after grafting the total neuronal density was higher than in normal cortex in both groups of intracortical grafts, but was lower than normal in the intraocular grafts. The numerical density of GABA-positive somata, however, decreased in all types of the grafts, and their ratio to GABA-negative neurons was significantly lower than in normal neocortical tissue. The total numerical density of the neurons in the grafts had strong positive correlation to the degree of morphological graft/host integration, which was evaluated as a ratio of extent of area of direct graft/host neuropil confluence versus the total extent of the border. The mean diameters of nuclei of GABA-negative cells in both groups of intracortical grafts did not differ from those of the intact neocortex, but in the isolated grafts they were substantially larger. Nuclei and somata of the GABA-positive cells, however, were hypertrophic in all groups of grafts, and especially in the intraocular ones. Measurements of the diameters of host neocortical neurons adjacent to the grafts also exhibited a less marked but still significant hypertrophy. The possible role of various factors (synaptic, trophic, functional), determining the described alterations in neuronal populations within the grafts is discussed.
Animals↗
Quantitative estimation of the ratio of GABA-immunoreactive cells in neocortical grafts.
Somatosensory anlage from 17-18 day old rat embryos were transplanted in place of the removed barrel cortex in adult rats. Six to eight months after transplantation, the grafts were either completely separated by glial scar or partly separated and partly confluent with the host neocortex. Each was studied histologically and immunostained for GABA. It was found that in partly confluent grafts the neuronal density was similar or even higher than in the host cortex, while the cell number in the separate grafts was much lower than in the nearby host cortex. The number of GABA-positive cells, however, was in all grafts significantly lower (2.9% on average) than in the normal cortex (11.8% on average). The decline in GABA-stained nerve cells was highest in separated grafts, but was somewhat less marked in transplants partly confluent with the host tissue. The possible role of partial or total deafferentation as well as the relative vulnerability of the transplanted tissue by temporary hypoxia and other metabolic disturbances are discussed as the probable factors in selective decline of GABA-ergic cells in the transplanted somatosensory cortex.
Animals↗
Age-related loss of GABA-positive and GABA-negative neurons in neocortical transplants.
The numerical density of GABA immunopositive and GABA immunonegative neurons was quantitatively determined in 0, 12, 30 and 90 day-old neocortical transplants, derived from E17 rat embryos and transplanted into adult hosts. It was found that the original, very high neuronal density in the fetal transplant declined steadily after transplantation to the somatosensory cortex of adult rat. The decline in numerical density of GABA-positive neurons, however, was disproportionately larger than that of GABA-negative nerve cells: At 90 days the proportion of GABA-positive cells was 2.3% (in contrast to the 11.8% in the adult host cortex). The density of GABA-negative neurons, on the other hand, remained slightly higher than comparable values in the control cortex. The decline in density of GABA-positive neurons was continuous until the 90th post-transplantation day, while final, close to normal density values of GABA-negative nerve cells were already reached in 30 day-old grafts, with no significant change afterwards.
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