Dentate Cells Research Articles

Proliferative Activity of Matrix Cells in the Lateral Ventricles and Granule Cells in the Dentate Gyrus of the Rat Hippocampus under Conditions of Pre- and Postnatal Alcohol Intoxication

The treatment of pregnant and lactating female rats with ethanol inhibits the proliferation of matrix cells in the lateral brain ventricles of fetuses and, during the early postnatal period, granule cells in the dentate gyrus and cells of the ventral horn of Ammon. A low proliferation rate leads to a decrease in the number of neurons forming the granule layer of the dentate gyrus and pyramidal neurons in the CA-1 field of the horn of Ammon.

Field responses to perforant path stimulation in the rat dentate gyrus: role of corticosterone and NMDA-receptor activation

Recent studies showed that corticosterone and NMDA receptor activation suppress cell turn-over in the dentate gyrus through a common pathway, the NMDA receptor acting downstream of the corticosteroids. The present data show that in the absence of corticosteroids but not of NMDA receptor activation synaptic responses of dentate cells are reduced. The reduced synaptic responsiveness in the absence of corticosterone is therefore probably not caused by changes in cell turn-over.

Detailed localization of aquaporin-4 messenger RNA in the CNS: preferential expression in periventricular organs

We have performed a detailed in situ hybridization study of the distribution of aquaporin-4 messenger RNA in the CNS. Contrary to expectation, we demonstrate that aquaporin-4 is ubiquitously expressed in the CNS. Strong hybridization labeling was detected in multiple olfactory areas, cortical cells, medial habenular nucleus, bed nucleus of the stria terminalis, tenia tecta, pial surface, pontine nucleus, hippocampal formation and multiple thalamic and hypothalamic areas. A low but significant hybridization signal was found, among others, in the choroid plexus of the lateral ventricles, ependymal cells, dorsal raphe and cerebellum. Overall, a preferential distribution of aquaporin-4 messenger RNA-expressing cells was evident in numerous periventricular organs. From the distribution study, the presence of aquaporin-4 messenger RNA-expressing cells in neuronal layers was evident in neuronal layers including the CA1–CA3 hippocampal pyramidal cells, granular dentate cells and cortical cells. Further evidence of neuronal expression comes from the semicircular arrangement of aquaporin-4 messenger RNA-expressing cells in the bed nucleus of the stria terminalis and medial habenular nucleus exhibiting Nissl-stained morphological features typical of neurons. Combined glial fibrillary acidic protein immunohistochemistry and aquaporin-4 messenger RNA in situ hybridization demonstrated that aquaporin-4 messenger RNA is expressed by glial fibrillary acidic protein-lacking cells. We conclude that aquaporin-4 messenger RNA is present in a collection of structures typically involved in the regulation of water and sodium intake and that aquaporin-4 water channels could be the osmosensor mechanism responsible for detecting changes in cell volume by these cells.

Persistent phosphorylation of cyclic amp responsive element-binding protein and activating transcription factor-2 transcription factors following transient cerebral ischemia in rat brain

The transcription factors cyclic AMP responsive element-binding protein (CREB) and activating transcription factor-2 were studied in rat brains subjected to 15 min ischemia followed by varied periods of reperfusion using western blot and immunocytochemical analyses. The total amounts of both CREB and activating transcription factor-2 were not altered in the hippocampus after ischemia. In contrast, levels of the phosphorylated forms of both transcription factors decreased during ischemia but rebounded following reperfusion. The phospho-forms of CREB and activating transcription factor-2 showed regional and temporal differences in their expression. Phospho-CREB was increased relative to control levels at 30 min, and continued to increase for at least three days postischemia, mainly in dentate granule cells. The level of phospho-activating transcription factor-2 appeared to be higher in CA1 pyramidal cells than in dentate granule cells after ischemia. The present findings suggest that the signaling pathways for phosphorylation of CREB may be neuroprotective for dentate cells, which are relatively resistant to ischemic insults. The increased phospho-activating transcription factor-2 may reflect increased stresses in these neurons. The more modest activation of CREB pathways in CAI neurons may not be enough to overcome the increased stresses in these neurons, contributing to delayed neuronal death.

Study on the Nootropic Mechanism of (-)Clausenamide - Influence on the Formation of Synapses in Mouse Brain

The effects of (-)clausenamide (claus) on brain development were studied. Sixty kunming strain weaning mice were divided into 4 groups. One group was served as control administered with normal saline, the other 3 groups were treated with (-)claus 5, 10 and 20mg kg−1 respectively by gavage once a day for 4 weeks. Results showed that (-)claus at dosage of 5 and 10 mg kg−1 facilitated learning and memory acquisition in step down and step through tests and increased thickness of cerebral cortex and synapse density significantly in the dentate cells over pyramidel cells in hippocampal region using quantitative technique of synapses analysis. These data provided the morphological basis of the nootropic effect of (-)claus.

Regionally specific induction of BDNF and truncated trkB.T1 receptors in the hippocampal formation after intraseptal injection of kainic acid

The septo-hippocampal cholinergic and GABAergic systems were lesioned with single unilateral injections of kainic acid (KA) into the septum to further characterize the role of these afferents in the regulation of hippocampal brain-derived neurotrophic factor (BDNF) expression. Nearly all cells expressing choline acetyltransferase, trkA or glutamic acid decarboxylase mRNA disappeared in the medial septum 7 days after the neurotoxin administration. The lesion resulted in a complete loss of CA3 pyramidal cells, and robust increases in BDNF mRNA levels in hippocampal granular dentate cells and in the amygdala. There were rapid transient increases of BDNF mRNA levels in the hippocampal formation and cortex. In addition, we found a strong induction of truncated trkB.T1 mRNA receptors in the stratum radiatum and stratum oriens of the CA3 subfield. The prolonged induction of BDNF mRNA levels suggests an important role of this neurotrophin, possibly mediated by truncated trkB receptors, in the regulation of hippocampal plasticity following injury.

Exposure to Predator Odor Reduces Locomotor Activity Levels in Adult Male Rats: Lack of Effect of Hippocampal Lesion

The hippocampus has been implicated in mediating responses to predators. Involvement of the hippocampus was tested in the present study in which a multivariate analysis of the locomotor activity of intact and hippocampectomized (destruction of dentate and CA1 cells) laboratory rats, Rattus norvegicus, was conducted following exposure to a predator odor. Levels of various activity variables were monitored in an automated activity monitoring system following a brief 3-min exposure to 2-propylthietane (weasel odor), caproic acid (goat odor), toluene (organic solvent), and a no-odor condition in hippocampal-lesioned (using colchicine) and sham-operated control male rats. Rats of both groups displayed reduced levels of total distance, movement time, vertical activity, and number of movements following exposure to weasel odor and toluene in comparison to the no-odor condition. Exposure to goal odor resulted only in reduced levels of vertical activity and number of movements. There were no differences in activity levels between hippocampal-lesioned and sham-operated rats during baseline activity recording or following exposure to any of the odors. However, hippocampal-lesioned rats spent less lime in the center of the activity boxes than sham-operated control rats across all conditions. This study demonstrates that laboratory rats show marked changes in locomotion in response to the odor of a predator and suggests that an intact hippocampus is not essential for mediating these responses.

Suppression by GABA B receptors of 4-aminopyridine-induced hyperactivity in guinea-pig dentate neurons

Double intracellular recording from granule cells and hilar neurons was performed in hippocampal slices to study the effect of γ-aminobutyric acid (GABA) receptor antagonists on the activity induced by the convulsant 4-aminopyridine (4-AP) in the dentate gyrus. 4-AP evoked GABA-mediated responses in granule cells and burst discharges in hilar neurons. In the presence of GABA B but not GABA A receptor antagonists, 4-AP evoked discharge activity in dentate granule cells. When both GABA A and GABA B receptors were blocked 4-AP induced synchronous ‘paroxysmal depolarizing shift’-like activity in granule cells and hilar neurons. Our data indicate that GABA B receptor-mediated mechanisms protect dentate cells against the convulsant effects of 4-AP

Synchronization of area CA3 hippocampal pyramidal cells and non-granule cells of the dentate gyrus in bicuculline-treated rat hippocampal slices

A recent study has described synchronous burst discharges of dentate hilar neurons and area CA3 pyramidal cells in the presence of the convulsants 4-aminopyridine and picrotoxin in guinea-pig hippocampal slices [Müller W. and Misgeld U. (1991) J. Neurophysiol. 65, 141–147]. To examine the synchronous activity of dentate cells and area CA3 pyramidal cells further, epileptiform burst discharges were examined in morphologically and/or electrophysiologically identified non-granule cells in the hilus and granule cell layer of the rat dentate gyrus and compared to simultaneously-recorded pyramidal cells of area CA3a, b, and c. Specifically, the types of dentate cells and the types of discharge were examined, as well as the timing of burst discharge of dentate cells relative to different cells of area CA3. In the presence of the GABA A receptor antagonist bicuculline (30 μM), all dentate cell types discharged in rhythmic, spontaneous bursts that were synchronized with area CA3 pyramidal cell epileptiform bursts. The sampled cells included hilar “mossy” cells, hilar fast-spiking cells (putative interneurons) as well as interneurons located in the granule cell layer, such as the pyramidal “basket” cells. Simultaneous recording from dentate non-granule cells and area CA3 pyramidal cells during exposure to bicuculline demonstrated that stimulus-evoked and spontaneous epileptiform bursts occurred almost exactly at the same time; there were only a few milliseconds between the onsets of pyramidal cell bursts and dentate cell bursts, with the pyramidal cell preceding the dentate cell in almost every case. There were no systematic differences among dentate cell types in the extent they lagged behind pyramidal cells, and there were no detectable differences among area CA3 pyramidal cells. In slices that were cut between area CA3 and the dentate gyrus, epileptiform bursts occurred in area CA3 but not in the dentate. These findings suggest that, in the absence of GABA A receptor-mediated inhibition, excitatory pathways from area CA3 to the dentate gyrus are strong and widespread. These pathways, and possibly other mechanisms, can lead to tightly synchronized action potential discharge of pyramidal cells and dentate non-granule cells. The results also suggest that disinhibition alone is insufficient to cause synchronous bursts in the dentate gyrus, in contrast to area CA3.

Responses of interposed and dentate neurons to perturbations of the locomotor cycle.

This study examined the relationship of antidromically identified neurons in the dentate and interposed nuclei to perturbed and unperturbed locomotion in the pre-collicular, mid-mamillary, decerebrate cat. During treadmill locomotion two methods were used to perturb the step cycle. In the first, the treadmill was braked in different phases of the step cycle, the "treadmill" perturbation. In the second, the motion of the ipsilateral forelimb was interrupted by a rod placed transiently in the limb's path, the "single limb" perturbation. Most interposed cells were modulated during locomotion, their discharge being highly correlated with the EMG of the ipsilateral biceps or triceps. When the locomotion was perturbed, the modulation ceased for the duration of the perturbation. A few interposed cells displayed activity patterns unrelated to the EMG but were responsive to perturbations of a single limb. These responses may be explained by the putative activation of peripheral afferents produced by the perturbation. Most dentate cells were not modulated during unperturbed locomotion but did respond to features of the treadmill perturbation. Usually the response was coupled to the resumption of treadmill motion. A minority of dentate neurons was modulated slightly during unperturbed locomotion. Their modulation was less dramatic than that of interposed cells and was only weakly related to limb movement or EMG activity. Like the interposed neurons, these dentate cells responded to the treadmill perturbation with a cessation of modulation. All dentate cells were unresponsive to single limb perturbations. In a preparation lacking cerebral cortical input, the findings show that neurons of the interposed and dentate nuclei are modulated differently during perturbed and unperturbed treadmill walking in the decerebrate cat. The activity of interposed neurons is related to specific features of EMG activity recorded from muscles in the ipsilateral forelimb. Although some dentate cells were weakly modulated during unperturbed locomotion, the majority of these neurons responded most dramatically to the occurrence of a perturbation which completely stopped the walking behavior.

Activity of dentate neurons during arm movements triggered by visual, auditory, and somesthetic stimuli in the monkey

Single-unit recordings were obtained from 404 neurons in the dentate and interposed nuclei in two monkeys trained to perform simple movements of the elbow in response to three different sensory cues: a light, a tone, and a small, brief perturbation of the trained forearm. Both flexion and extension movements were investigated. Those dentate neurons that showed a clear modulation before the onset of movement (149 of 318 cells recorded) were classified as stimulus related or movement related on the basis of an analysis of the timing of the initial change in discharge. Seventy-one percent of these dentate neurons (106/149) were classified as stimulus related, and 21% (31/149) were classified as movement related. Within the stimulus-related group 87% responded selectively to only one or two of the sensory cues (selective stimulus-related neurons), most often the teleceptive cues, whereas the remaining 13% responded nonselectively to all three cues (nonselective stimulus-related neurons). Interposed neurons, in contrast, showed principally movement-related discharge, and this represented the initial change in discharge in 89% of the neurons. Eleven percent of the interposed cells showed a selective response to the somesthetic cue. The discharge of 28 out of 91 dentate neurons tested with both flexion and extension movements varied with the direction of movement. Few dentate neurons (9%) were found to display any direction sensitivity when considering the discharge preceding the onset of movement, and none of these showed a reciprocal pattern. The discharge of a greater proportion of neurons (24%) was direction sensitive during movement and was occasionally reciprocal. In the same monkeys, however, 78% of the neurons in the neighboring interposed nucleus were direction sensitive, and one-quarter of these displayed reciprocal patterns of discharge. Thus, the discharge of dentate neurons, occurring well in advance of a conditioned movement, cannot specify direction in this simple reaction-time (RT) task. The sensory responses of selective stimulus-related dentate cells ended near the onset of movement but were time locked to the stimulus and not to the movement. When a neuron was responsive to two of the cues the response did not vary with the modality of the stimulus apart from changes in the latency. The initial sensory response was usually followed by later "secondary" changes in discharge that were temporally related to the movement.(ABSTRACT TRUNCATED AT 250 WORDS)

THE ANION SELECTIVITY OF GABA‐MEDIATED POST‐SYNAPTIC POTENTIALS IN MOUSE HIPPOCAMPAL CELLS

Intracellular recordings were made from CA1 and dentate cells of the mouse hippocampal slice. When potassium acetate was used to fill the electrodes, spontaneous synaptic activity was rarely seen in CA1 or dentate cells. In contrast, when electrodes filled with potassium chloride were used, spontaneous depolarizing post-synaptic potentials (p.s.p.s) were prominent. That these p.s.p.s were mediated by gamma-aminobutyric acid (GABA) was supported by the following: they were blocked by electrophoretic application of bicuculline methiodide; their appearance was associated with the reversal of the evoked GABA-mediated recurrent inhibitory post-synaptic potential (i.p.s.p.) and their appearance was associated with the positive displacement of the reversal potential for the response to GABA applied by electrophoresis close to the cell soma. The interval distribution for the p.s.p.s could not be fitted by a Poisson distribution. The anionic selectivity of the conductance evoked by GABA was investigated by using the potassium salts of a range of anions to fill the electrodes. Depolarizing spontaneous p.s.p.s were seen in all cells impaled with electrodes containing potassium chloride, iodide, bromide, nitrate, or chlorate. In these cells, the reversal potential for the response to electrophoretically applied GABA was displaced in the depolarizing direction and the evoked recurrent i.p.s.p. was reversed. When anions with hydrated shells larger than chlorate (bicarbonate, sulphate, chromate, acetate or citrate) were used, spontaneous depolarizing p.s.p.s were not seen, and the reversal potential for the response to somatic GABA application and for the evoked recurrent i.p.s.p. lay between -70 and -75 mV.

Actions and interactions of GABA and benzodiazepines in the mouse hippocampal slice.

Intracellular recordings have been made from CA1, CA3 and dentate cells of the mouse hippocampal slice. Gamma-aminobutyric acid (GABA) and the water-soluble benzodiazepines, midazolam and flurazepam were applied close to the impaled cell somata by microelectrophoresis. GABA always caused a fall in input resistance, although the associated changes in membrane potential were variable. These were consistent with reports which have defined a hyperpolarizing response to somatic and a depolarizing response to dendritic application of GABA to CA1 and CA3 cells in the rat and guinea-pig. In this study, the phenomenon was seen in CA1, CA3 and dentate cells. The reversal potential for the hyperpolarizing, somatic response to GABA lay between -70 and -75 mV, similar to the reversal potential of the evoked recurrent inhibitory post-synaptic potential (i.p.s.p.). The change in cell input conductance caused by GABA was larger at membrane potentials positive to the resting potential and smaller at hyperpolarized membrane potentials. Extracellular recordings of action potential frequency were made from ten cells in which the application of either midazolam or flurazepam increased the inhibitory potency of GABA. In three of these cells, the benzodiazepine reduced action potential frequency slightly when applied alone. Neither midazolam nor flurazepam had a consistent effect on membrane potential, resting input resistance or the current-voltage (I-V) relations of the cells when ejected alone. In twenty-eight of forty-one cells examined in detail, ejection of either midazolam or flurazepam was found to increase the response to GABA. In six cells, the response to GABA was significantly reduced by the benzodiazepine tested whilst in the remainder, no interaction of the drugs could be demonstrated. Examination of the dose-response relation for GABA alone and in the presence of midazolam or flurazepam showed that the maximal response to GABA was increased by the benzodiazepine in some cells while it was unchanged in others. When intracellular electrodes were filled with potassium chloride, spontaneous depolarizing GABA-mediated post-synaptic potentials (p.s.p.s) were seen. Measurement of the interval and amplitude distributions of these events showed that flurazepam increased their amplitude but not their frequency.

An intracellular study of dentate, CA1 and CA3 neurones in the mouse hippocampal slice.

Intracellular recordings were made from CA1 and CA3 pyramidal cells and from dentate granule cells of the mouse hippocampal slice preparation. The passive electrical properties of the cells and their responses to electrical stimulation of the major antidromic and orthodromic pathways were explored. The majority of cells were impaled between 60 and 100 micron from the surface of the slice. Mean resting potentials were about -66 mV for dentate and CA1 cells and -61 mV for CA3 cells. Mean input resistances were 87, 78 and 73 M omega respectively, with a range of 30-160 M omega for all three populations. Action potential amplitudes ranged from 70 to 110 mV and were typically about 90 mV. Current-voltage (I-V) plots for all three populations were ohmic within a range 10-20 mV negative to the resting potentials. The chord resistance of the I-V relation was lower at more negative potentials and higher at more positive potentials than at the resting potential. Antidromic stimulation at intensities subthreshold for action potential invasion of the impaled cell gave rise to inhibitory post-synaptic potentials (i.p.s.p.s) in CA1 and CA3 cells. The reversal potential of the i.p.s.p.s lay between -65 and -75 mV. They were chloride dependent and could be attenuated by application of bicuculline methiodide. No recurrent i.p.s.p. was seen in dentate cells when using potassium-acetate-filled electrodes. If potassium-chloride-filled intracellular electrodes were used, thus raising the intracellular chloride ion concentration, an antidromically evoked, bicuculline-sensitive depolarizing post-synaptic potential (p.s.p.) could be evoked. Thus, a gamma-aminobutyric acid (GABA)-mediated recurrent inhibitory pathway was present in the slice in all three cell populations but appeared to be difficult to evoke reliably in the dentate gyrus. Orthodromic excitation of CA1 and CA3 cells evoked an excitatory post-synaptic potential (e.p.s.p.) followed by a biphasic hyperpolarization. The early hyperpolarization, lasting about 50 ms, reversed at about -65 mV and was chloride dependent. The later hyperpolarization lasted up to 400 ms, reversed at about -85 mV, and was chloride independent. The e.p.s.p. evoked in dentate cells by stimulation of the perforant path was biphasic and was followed by a hyperpolarization lasting 300-600 ms. The hyperpolarization resembled the late hyperpolarization described above. The two components of the e.p.s.p. may have been produced by the combined activation of the medial and lateral components of the perforant path. Small-amplitude regenerative potentials have been seen in all three cell types.(ABSTRACT TRUNCATED AT 400 WORDS)

Convergence of cerebral inputs onto dentate neurons in monkey

The patterns of convergence of inputs from different areas of the cerebral cortex and the peripheral nerves onto single dentate neurons was studied in cebus monkeys. Dentate neurons receive their strongest and most numerous inputs from the premotor and supplementary motor regions of area 6. The sensorimotor and frontal cortices have weaker projections to the dentate nucleus, while peripheral nerves and many other association cortical areas were found to be effective in influencing cells of the lateral cerebellum. Dentate cells that respond to stimulation of hindlimb regions of the sensorimotor cortex tend to receive their principal input from the supplementary motor area and medial premotor regions, while neurons responding to forelimb sensorimotor cortex tend to receive lateral premotor inputs. In addition there is a topographical organization within the ventral pole of dentate with the hindlimb represented in the anterior regions and the forelimb in the posterior regions. These results are compared with those of similar studies of interpositus and dentate neurons in cat and monkey. The differences between the afferent inputs to dentate and interpositus are consistent with the suggestion that the lateral cerebellum is involved in programming movement parameters before movement initiation while the intermediate zone is involved in up-dating the evolving movement.