Neuronal Diversity in GABAergic Long-Range Projections from the Hippocampus

Jinno, Shozo; Klausberger, Thomas; Márton, Lőrinc; Dalezios, Yannis; Roberts, J. D. B.; Fuentealba, Pablo; Bushong, Eric A.; Henze, Darrell A.; Buzsáki, György; Somogyi, Péter

doi:10.1523/jneurosci.1847-07.2007

Cited by 319 publications

(442 citation statements)

References 55 publications

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“…The hippocampus CA3 has enriched GABAergic inputs and outputs, whereas the serotoninergic and dopaminergic neurons are scarcely seen. 55,56 Our data further validate that the CA3 accumulation of htau may specifically disrupt the local neural metabolisms and the functions with no influence on serotonergic or dopaminergic input from other brain regions.…”

Section: Discussionsupporting

confidence: 67%

Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice

Wang

Tan

et al. 2017

Molecular Therapy

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Patients with Alzheimer's disease (AD) commonly show anxiety behaviors, but the molecular mechanisms are not clear and no efficient intervention exists. Here, we found that overexpression of human wild-type, full-length tau (termed htau) in hippocampus significantly decreased the extracellular g-aminobutyric acid (GABA) level with inhibition of g oscillation and the evoked inhibitory postsynaptic potential (eIPSP). With tau accumulation, the mice show age-dependent anxiety behaviors. Among the factors responsible for GABA synthesis, release, uptake, and transport, we found that accumulation of htau selectively suppressed expression of the intracellular vesicular GABA transporter (vGAT). Tau accumulation increased miR92a, which targeted vGAT mRNA 3 0 UTR and inhibited vGAT translation. Importantly, we found that upregulating GABA tones by intraperitoneal injection of midazolam (a GABA agonist), ChR2-mediated photostimulating and overexpressing vGAT, or blocking miR92a by using specific antagomir or inhibitor efficiently rescued the htau-induced GABAergic dysfunctions with attenuation of anxiety. Finally, we also demonstrated that vGAT level decreased while the miR92a increased in the AD brains. These findings demonstrate that the AD-like tau accumulation induces anxiety through disrupting miR92a-vGAT-GABA signaling, which reveals molecular mechanisms underlying the anxiety behavior in AD patients and potentially leads to the development of new therapeutics for tauopathies.

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Section: Discussionsupporting

confidence: 67%

Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice

Wang

Tan

et al. 2017

Molecular Therapy

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“…Finally, although we have not investigated directly how hippocamposeptal interneurons behave during carbachol oscillations, a previous study has shown that st. oriens-alveus interneurons (which includes some of the neurons projecting to the septum) fire single spikes phase locked to the field in carbachol and are likely activated by recurrent excitation from pyramidal neurons (McMahon et al, 1998;Hajos et al, 2004). An elegant report recently showed that identified st. oriens-alveus hippocamposeptal neurons also fire at low frequency phase locked to theta in vivo and at a similar phase than pyramidal neurons (Jinno et al, 2007). Together, these reports suggest that hippocamposeptal GABA neurons are active during carbachol or theta oscillations and are phase locked to pyramidal cells.…”

Section: Discussionmentioning

confidence: 66%

The Hippocamposeptal Pathway Generates Rhythmic Firing of GABAergic Neurons in the Medial Septum and Diagonal Bands: An Investigation Using a Complete Septohippocampal PreparationIn Vitro

Manseau¹,

Goutagny²,

Danik³

et al. 2008

J. Neurosci.

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The medial septum diagonal band area (MS/DB) projects to the hippocampus through the fornix/fimbria pathway and is implicated in generating hippocampal theta oscillations. The hippocampus also projects back to the MS/DB, but very little is known functionally about this input. Here, we investigated the physiological role of hippocamposeptal feedback to the MS/DB in a complete in vitro septohippocampal preparation containing the intact interconnecting fornix/fimbria pathway. We demonstrated that carbachol-induced rhythmic thetalike hippocampal oscillations recorded extracellularly were synchronized with powerful rhythmic IPSPs in whole-cell recorded MS/DB neurons. Interestingly, we found that these IPSPs evoked rebound spiking in GABAergic MS/DB neurons. In contrast, putative cholinergic and glutamatergic MS/DB neurons responded only weakly with rebound spiking and, as a result, were mostly silent during theta-like oscillations. We next determined the mechanism underlying the rebound spiking that followed the IPSPs in MS/DB GABAergic neurons using phasic electrical stimulation of the fornix/fimbria pathway. We demonstrate that the increased rebound spiking was attributable to the activation of I h current, because it was significantly reduced by low concentrations of the I h antagonist ZD7288 [4-(N-ethyl-Nphenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride]. Together, these results suggest that rhythmical activity in hippocampus is transferred to the MS/DB and can preferentially phase the spiking of GABAergic MS/DB neurons because of their significant expression of I h currents. Our data demonstrate that hippocamposeptal inhibition facilitates theta rhythmic discharges in MS/DB GABAergic neurons while favoring the inhibition of most ACh and glutamate neurons.

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“…5). SLCs are GABAergic cells that project mainly to the medial septum and possess relatively few local axon collaterals near the cell body (Gulyás et al, 1992;Jinno et al, 2007;Takács et al, 2008). One of the main characteristics of SLCs is that, in contrast to other GABAergic cells in this study, the primary dendrites of SLCs are aligned with and largely restricted to stratum lucidum (and, to a lesser extent, pyramidale), and the dendrites are densely covered with large numbers of dendritic spines (Fig.…”

Section: Specific Description Of Cell Typesmentioning

confidence: 81%

“…2 A, asterisk). Like most other projecting GABAergic cell types (Jinno et al, 2007), the vast majority of SLCs were positive for SOM (24 of 26 tested SLCs) and for NPY (7 of 7), but not for CCK (0 of 17) and PV (0 of 6). Note that we were not able to reliably test for the presence of calretinin, which is another marker for SLCs, most likely because of wash-out of intracellular constituents from postsynaptic cells during the long-lasting somatic recordings.…”

Section: Specific Description Of Cell Typesmentioning

confidence: 89%

Functional Specificity of Mossy Fiber Innervation of GABAergic Cells in the Hippocampus

Szabadics¹,

Soltész²

2009

J. Neurosci.

105

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One million mossy fibers in the rat provide individually sparse but functionally important synaptic connections between the dentate gyrus and hippocampus. Although the majority of mossy fiber targets are GABAergic cells, the functional organization of the feedforward GABAergic machinery modulating the interactions of granule cells and CA3 pyramidal cells are not yet understood. We used mossy fiber bouton to GABA neuron paired recordings in the CA3 to demonstrate that mossy fibers provide cell type-specific innervation to distinct GABAergic neurons with specialized intra-and extrahippocampal outputs. Our results show that mossy fibers contact the perisomatically projecting fast-spiking and regular-spiking basket cells, in addition to the dendritically projecting ivy cells, and the septum-projecting spiny stratum lucidum cells. Monosynaptic mossy fiber inputs to fast-spiking basket cells and spiny stratum lucidum cells were found to be numerous, but they were small in amplitude and displayed low transmission probabilities. In contrast, regular-spiking basket cells and ivy cells were less likely to be innervated by mossy fibers, but the amplitudes of mossy fiber EPSCs were large and the transmission probabilities were high. The dependence of the numbers and strengths of the mossy fiber inputs to CA3 GABAergic cells on the postsynaptic cell type was correlated with the frequency of the background synaptic events, so that cells with weak but numerous mossy fiber inputs received high rates of spontaneous synaptic events. Together, these results reveal the diverse components and high degree of functional specificity of the GABAergic cellular machinery underlying the dentate gyrus-CA3 interface.

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Neuronal Diversity in GABAergic Long-Range Projections from the Hippocampus

Cited by 319 publications

References 55 publications

Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice

Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice

The Hippocamposeptal Pathway Generates Rhythmic Firing of GABAergic Neurons in the Medial Septum and Diagonal Bands: An Investigation Using a Complete Septohippocampal PreparationIn Vitro

Functional Specificity of Mossy Fiber Innervation of GABAergic Cells in the Hippocampus

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