Parvalbumin Interneurons of Hippocampus Tune Population Activity at Theta Frequency

SummaryHippocampal theta rhythm arises from a combination of recently described intrinsic theta oscillators and inputs from multiple brain areas. Interneurons expressing the markers parvalbumin (PV) and somatostatin (SOM) are leading candidates to participate in intrinsic rhythm generation and principal cell (PC) coordination in distal CA1 and subiculum. We tested their involvement by optogenetically activating and silencing PV or SOM interneurons in an intact hippocampus preparation that preserves intrinsic connections and oscillates spontaneously at theta frequencies. Despite evidence suggesting that SOM interneurons are crucial for theta, optogenetic manipulation of these interneurons modestly influenced theta rhythm. However, SOM interneurons were able to strongly modulate temporoammonic inputs. In contrast, activation of PV interneurons powerfully controlled PC network and rhythm generation optimally at 8 Hz, while continuously silencing them disrupted theta. Our results thus demonstrate a pivotal role of PV but not SOM interneurons for PC synchronization and the emergence of intrinsic hippocampal theta

Electrophysiological and Morphological Characterization of Chrna2 Cells in the Subiculum and CA1 of the Hippocampus: An Optogenetic Investigation

The nicotinic acetylcholine receptor alpha2 subunit (Chrna2) is a specific marker for oriens lacunosum-moleculare (OLM) interneurons in the dorsal CA1 region of the hippocampus. It was recently shown using a Chrna2-cre mice line that OLM interneurons can modulate entorhinal cortex and CA3 inputs and may therefore have an important role in gating, encoding, and recall of memory. In this study, we have used a combination of electrophysiology and optogenetics using Chrna2-cre mice to determine the role of Chrna2 interneurons in the subiculum area, the main output region of the hippocampus. We aimed to assess the similarities between Chrna2 subiculum and CA1 neurons in terms of the expression of interneuron markers, their membrane properties, and their inhibitory input to pyramidal neurons. We found that subiculum and CA1 dorsal Chrna2 cells similarly expressed the marker somatostatin and had comparable membrane and firing properties. The somas of Chrna2 cells in both regions were found in the deepest layer with axons projecting superficially. However, subiculum Chrna2 cells displayed more extensive projections with dendrites which occupied a significantly larger area than in CA1. The post-synaptic responses elicited by Chrna2 cells in pyramidal cells of both regions revealed comparable inhibitory responses elicited by GABAA receptors and, interestingly, GABAB receptor mediated components. This study provides the first in-depth characterization of Chrna2 cells in the subiculum, and suggests that subiculum and CA1 Chrna2 cells are generally similar and may play comparable roles in both sub-regions

Modulation intra-synaptique des neurotransmissions cholinergique et sérotoninergique par le glutamate via VGLUT3 (transporteur vésiculaire du glutamate de type 3)

Les transporteurs vésiculaires du glutamate ou VGLUTs permettent l accumulation du glutamate dans les vésicules synaptiques. Trois VGLUTs différents ont été identifiés, VGLUT1, 2 et 3. VGLUT3 se révèle comme étant atypique puisqu il est présent dans des sous-populations de neurones préalablement définis comme non-glutamatergiques. L objectif principal de ma thèse a été de déterminer la fonction de VGLUT3 dans les interneurones cholinergiques du striatum, et les neurones sérotoninergiques des noyaux du raphé. Le support principal de ce travail est la caractérisation d une lignée de souris mutantes n exprimant plus VGLUT3 (souris Vglut3 / ). Dans les interneurones cholinergiques striataux, VGLUT3 est présent sur les mêmes vésicules que VAChT (transporteur vésiculaire de l acétylcholine). Le transport de glutamate via VGLUT3 permet une potentialisation de l accumulation vésiculaire d acétylcholine, et donc une modulation positive du quantum cholinergique. L étude de VGLUT3 dans le système sérotoninergique a révélé une hétérogénéité anatomique importante des projections sérotoninergiques dans certaines structures limbiques. Le transport de glutamate via VGLUT3 dans certaines terminaisons du système sérotoninergique permet une potentialisation de la capture de sérotonine. L ensemble des résultats obtenus au cours de ma thèse a permis de mettre en évidence un nouveau mécanisme de régulation du quantum vésiculaire. Ce mécanisme, nommé synergie vésiculaire , a dévoilé un rôle supplémentaire et inattendu du glutamate : la modulation intra-synaptique du transport vésiculaire de neurotransmetteurs classiques du système nerveux central.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Simple, biologically-constrained CA1 pyramidal cell models using an intact, whole hippocampus context [v2; ref status: indexed, http://f1000r.es/5fu]

The hippocampus is a heavily studied brain structure due to its involvement in learning and memory. Detailed models of excitatory, pyramidal cells in hippocampus have been developed using a range of experimental data. These models have been used to help us understand, for example, the effects of synaptic integration and voltage gated channel densities and distributions on cellular responses. However, these cellular outputs need to be considered from the perspective of the networks in which they are embedded. Using modeling approaches, if cellular representations are too detailed, it quickly becomes computationally unwieldy to explore large network simulations. Thus, simple models are preferable, but at the same time they need to have a clear, experimental basis so as to allow physiologically based understandings to emerge. In this article, we describe the development of simple models of CA1 pyramidal cells, as derived in a well-defined experimental context of an intact, whole hippocampus preparation expressing population oscillations. These models are based on the intrinsic properties and frequency-current profiles of CA1 pyramidal cells, and can be used to build, fully examine, and analyze large networks