Connection matrix of the hippocampal formation: I. The dentate gyrus

Patton, Paul; McNaughton, Bruce L.

doi:10.1002/hipo.450050402

Cited by 112 publications

(85 citation statements)

References 342 publications

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“…3. Consistent with previous estimates (21,22), there were approximately 1.2 million neurons in the granule cell layer, 225,000 neurons in CA3/2, and 390,000 neurons in the CAl field of the hippocampus. Neuron number failed to differ, however, as a function of either chronological age or cognitive status.…”

Section: Resultssupporting

confidence: 89%

Preserved neuron number in the hippocampus of aged rats with spatial learning deficits.

Rapp

Gallagher

1996

Proc. Natl. Acad. Sci. U.S.A.

584

327

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Hippocampal neuron loss is widely viewed as a hallmark of normal aging. Moreover, neuronal degeneration is thought to contribute directly to age-related deficits in learning and memory supported by the hippocampus. By taking advantage of improved methods for quantifying neuron number, the present study reports evidence challenging these long-standing concepts. The status of hippocampal-dependent spatial learning was evaluated in young and aged Long-Evans rats using the Morris water maze, and the total number of neurons in the principal cell layers of the dentate gyrus and hippocampus was quantified according to the optical fractionator technique. For each of the hippocampal fields, neuron number was preserved in the aged subjects as a group and in aged individuals with documented learning and memory deficits indicative of hippocampal dysfunction. The findings demonstrate that hippocampal neuronal degeneration is not an inevitable consequence of normal aging and that a loss of principal neurons in the hippocampus fails to account for age-related learning and memory impairment. The observed preservation of neuron number represents an essential foundation for identifying the neurobiological effects of hippocampal aging that account for cognitive decline.A substantial body of research conducted over the last two decades in rats, monkeys, and humans has led to the view that the hippocampus is particularly susceptible to neuronal degeneration during normal aging (1). Based on this background it seems reasonable to suppose that neuron loss might be responsible for deficits in hippocampal-dependent learning and memory associated with advanced age (2-7). An important source of evidence consistent with this proposal derives from studies examining hippocampal neuron density in rat models of age-related learning and memory impairment. Earlier reports, for example, demonstrated that pyramidal cell density in the hippocampus decreases by more than 30% in aged Long-Evans rats with learning and memory deficits indicative of hippocampal dysfunction but that neuron density is less affected among aged subjects with preserved learning and memory (8). In addition, perinatal manipulations that prevent age-related declines in hippocampal cell density also protect against age-related spatial learning deficits (9). Thus, these observations have prompted intensive efforts to define the cell biological mechanisms responsible for age-related neuronal death in the hippocampus (2, 4-9).Recent advances in the field of stereology have made it possible to determine with greater precision the magnitude of neuronal degeneration in the aged hippocampus and to document statistical relationships between neuron loss and agerelated learning and memory impairment (10,11). In contrast to measures of neuron density, modern stereological methods are specifically aimed at providing estimates of total neuron number in a region of interest. The primary advantage of this approach for research on aging is that neuron number represents an unequivocal pa...

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Section: Resultssupporting

confidence: 89%

Preserved neuron number in the hippocampus of aged rats with spatial learning deficits.

Rapp

Gallagher

1996

Proc. Natl. Acad. Sci. U.S.A.

584

327

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“…Second, mossy cells display spontaneous firing at rest both in vitro [4.5 Ϯ 1.9 Hz in Ishizuka and Kosaka (1998); from our experiments, mossy cells recorded in noninvasive cell-attached mode: 2.51 Ϯ 2.5 Hz; n ϭ 4 cells; data not shown] and in vivo [0.8 Ϯ 0.2 Hz in Soltesz et al (1993)]. The convergence of many mossy cells onto a single granule cell (Patton and McNaughton, 1995) suggests that spontaneous mossy cell firing could provide tonic excitation to granule cells, the removal of which by the mossy cell ablations may have contributed to the decrease in population spikes. It is interesting to note that the population spikes appeared to be more sensitive to both mossy cell and interneuron ablations compared with fEPSPs in all experiments performed in horizontal slices (Fig.…”

Section: Contribution Of Mossy Cells To Granule Cell Excitabilitymentioning

confidence: 72%

Rapid Deletion of Mossy Cells Does Not Result in a Hyperexcitable Dentate Gyrus: Implications for Epileptogenesis

Ratzliff¹,

Howard²,

Santhakumar³

et al. 2004

J. Neurosci.

109

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Loss of cells from the hilus of the dentate gyrus is a major histological hallmark of human temporal lobe epilepsy. Hilar mossy cells, in particular, are thought to show dramatic numerical reductions in pathological conditions, and one prominent theory of epileptogenesis is based on the assumption that mossy cell loss directly results in granule cell hyperexcitability. However, whether it is the disappearance of hilar mossy cells from the dentate gyrus circuitry after various insults or the subsequent synaptic-cellular alterations (e.g., reactive axonal sprouting) that lead to dentate hyperexcitability has not been rigorously tested, because of the lack of available techniques to rapidly remove specific classes of nonprincipal cells from neuronal networks.We developed a fast, cell-specific ablation technique that allowed the targeted lesioning of either mossy cells or GABAergic interneurons in horizontal as well as axial (longitudinal) slices of the hippocampus. The results demonstrate that mossy cell deletion consistently decreased the excitability of granule cells to perforant path stimulation both within and outside of the lamella where the mossy cell ablation took place. In contrast, ablation of interneurons caused the expected increase in excitability, and control aspirations of the hilar neuropil or of interneurons in the presence of GABA receptor blockers caused no alteration in granule cell excitability.These data do not support the hypothesis that loss of mossy cells from the dentate hilus after seizures or traumatic brain injury directly results in hyperexcitability.

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“…Another possibility is that the marked increase in the frequency of mIPSCs from Ϸ1 Hz to Ϸ9 Hz leads to a partial depression of transmitter release, such that the depression of evoked release became partially occluded. However, this hypothesis is incompatible with divergence and convergence in BC-GC microcircuits (38). If the dentate gyrus contains Ϸ20,000 BCs and Ϸ1,000,000 GCs, and if a BC contacts Ϸ2,500 GCs, a GC would receive convergent input from Ϸ50 BCs.…”

Section: Discussionmentioning

confidence: 99%

Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses

Kerr

Reisinger

Jónás

2008

Proc. Natl. Acad. Sci. U.S.A.

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Previous studies revealed that synaptotagmin 1 is the major Ca 2؉ sensor for fast synchronous transmitter release at excitatory synapses. However, the molecular identity of the Ca 2؉ sensor at hippocampal inhibitory synapses has not been determined. To address the functional role of synaptotagmin 1 at identified inhibitory terminals, we made paired recordings from synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus in organotypic slice cultures from wild-type and synaptotagmin 1-deficient mice. As expected, genetic elimination of synaptotagmin 1 abolished synchronous transmitter release at excitatory GC-BC synapses. However, synchronous release at inhibitory BC-GC synapses was maintained. Quantitative analysis revealed that elimination of synaptotagmin 1 reduced release probability and depression but maintained the synchrony of transmitter release at BC-GC synapses. Elimination of synaptotagmin 1 also increased the frequency of both miniature excitatory postsynaptic currents (measured in BCs) and miniature inhibitory postsynaptic currents (recorded in GCs), consistent with a clamping function of synaptotagmin 1 at both excitatory and inhibitory terminals. Single-cell reverse-transcription quantitative PCR analysis revealed that single BCs coexpressed multiple synaptotagmin isoforms, including synaptotagmin 1-5, 7, and 11-13. Our results indicate that, in contrast to excitatory synapses, synaptotagmin 1 is not absolutely required for synchronous release at inhibitory BC-GC synapses. Thus, alternative fast Ca 2؉ sensors contribute to synchronous release of the inhibitory transmitter GABA in cortical circuits.GABAergic interneurons ͉ basket cells ͉ hippocampus ͉ Ca 2ϩ sensor G ABAergic interneurons of the basket cell subtype (BCs) play a key role in neuronal network function. These interneurons control the average activity level in principal neurons via fast feed-forward and feedback inhibition (1) and are involved in the generation of network oscillations in the ␥-frequency range (2). BCs receive a fast excitatory synaptic input, which allows them to detect coincident activity of principal neurons (3). Furthermore, BCs generate rapid inhibitory output signals in their target cells (4). Previous studies revealed that transmitter release at BC output synapses is exclusively mediated by P/Q-type Ca 2ϩ channels (5, 6) and that these Ca 2ϩ channels are tightly coupled to the Ca 2ϩ sensors of exocytosis, with coupling distances of 10-20 nm (7). Tight coupling contributes to fast signaling, increasing the speed and temporal precision of transmitter release.Expression of specialized Ca 2ϩ sensors of exocytosis may also contribute to the speed and temporal precision of synaptic transmission. However, the synaptic Ca 2ϩ sensors that mediate glutamatergic BC input and GABAergic BC output have not yet been identified. At several synapses, synaptotagmin 1 is essential for fast transmitter release (8-11). Genetic elimination of synaptotagmin 1 abolishes synchronous release in both glutamatergi...

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Connection matrix of the hippocampal formation: I. The dentate gyrus

Cited by 112 publications

References 342 publications

Preserved neuron number in the hippocampus of aged rats with spatial learning deficits.

Preserved neuron number in the hippocampus of aged rats with spatial learning deficits.

Rapid Deletion of Mossy Cells Does Not Result in a Hyperexcitable Dentate Gyrus: Implications for Epileptogenesis

Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses

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