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Appetite suppressive role of medial septal glutamatergic neurons.

ABSTRACT: Feeding behavior is controlled by diverse neurons and neural circuits primarily concentrated in the hypothalamus and hindbrain in mammals. In this study, by using chemo/optogenetic techniques along with feeding assays, we investigate how neurons within the medial septal complex (MSc), a brain area implicated in emotion and cognition, contribute to food intake. We find that chemo/optogenetic activation of MSc glutamatergic neurons profoundly reduces food intake during both light and dark periods of the rodent light cycle. Furthermore, we find that selective activation of MSc glutamatergic projections in paraventricular hypothalamus (PVH) reduces food intake, suggesting that MSc glutamatergic neurons suppress feeding by activating downstream neurons in the PVH. Open-field behavioral assays reveal that these neurons do not overtly affect anxiety levels and locomotion. Collectively, our findings demonstrate that septal glutamatergic neurons exert anorexigenic effects by projecting to the PVH without affecting anxiety and physical activities.

SUBMITTER: Sweeney P

PROVIDER: S-EPMC5748170 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Appetite suppressive role of medial septal glutamatergic neurons.

Sweeney Patrick P Li Changhong C Yang Yunlei Y

Proceedings of the National Academy of Sciences of the United States of America 20171211 52

Feeding behavior is controlled by diverse neurons and neural circuits primarily concentrated in the hypothalamus and hindbrain in mammals. In this study, by using chemo/optogenetic techniques along with feeding assays, we investigate how neurons within the medial septal complex (MSc), a brain area implicated in emotion and cognition, contribute to food intake. We find that chemo/optogenetic activation of MSc glutamatergic neurons profoundly reduces food intake during both light and dark periods ...[more]

PMID: 29229861

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Project description:The medial septum implements cortical theta oscillations, a 5-12 Hz rhythm associated with locomotion and paradoxical sleep reflecting synchronization of neuronal assemblies such as place cell sequence coding. Highly rhythmic burst-firing parvalbumin-positive GABAergic medial septal neurons are strongly coupled to theta oscillations and target cortical GABAergic interneurons, contributing to coordination within one or several cortical regions. However, a large population of medial septal neurons of unidentified neurotransmitter phenotype and with unknown axonal target areas fire with a low degree of rhythmicity. We investigated whether low-rhythmic-firing neurons (LRNs) innervated similar or different cortical regions to high-rhythmic-firing neurons (HRNs) and assessed their temporal dynamics in awake male mice. The majority of LRNs were GABAergic and parvalbumin-immunonegative, some expressing calbindin; they innervated interneurons mostly in the dentate gyrus (DG) and CA3. Individual LRNs showed several distinct firing patterns during immobility and locomotion, forming a parallel inhibitory stream for the modulation of cortical interneurons. Despite their fluctuating firing rates, the preferred firing phase of LRNs during theta oscillations matched the highest firing probability phase of principal cells in the DG and CA3. In addition, as a population, LRNs were markedly suppressed during hippocampal sharp-wave ripples, had a low burst incidence, and several of them did not fire on all theta cycles. Therefore, CA3 receives GABAergic input from both HRNs and LRNs, but the DG receives mainly LRN input. We propose that distinct GABAergic LRNs contribute to changing the excitability of the DG and CA3 during memory discrimination via transient disinhibition of principal cells.SIGNIFICANCE STATEMENT For the encoding and recall of episodic memories, nerve cells in the cerebral cortex are activated in precisely timed sequences. Rhythmicity facilitates the coordination of neuronal activity and these rhythms are detected as oscillations of different frequencies such as 5-12 Hz theta oscillations. Degradation of these rhythms, such as through neurodegeneration, causes memory deficits. The medial septum, a part of the basal forebrain that innervates the hippocampal formation, contains high- and low-rhythmic-firing neurons (HRNs and LRNs, respectively), which may contribute differentially to cortical neuronal coordination. We discovered that GABAergic LRNs preferentially innervate the dentate gyrus and the CA3 area of the hippocampus, regions important for episodic memory. These neurons act in parallel with the HRNs mostly via transient inhibition of inhibitory neurons.

Project description:Social hierarchy greatly impacts physical and mental health, but the relationship between social hierarchy and depression/anxiety and the underlying neural mechanism remain unclear. The present study used the tube test to determine the social hierarchy status of mice and then performed several behavioral tests to evaluate depression-like and anxiety-like behaviors. Electrophysiological techniques were used to record the firing activities of glutamatergic pyramidal neurons and local field potentials in the medial prefrontal cortex (mPFC). The results suggested that the mice in each cage (4 per cage) established a stable social hierarchy after 2 weeks. Subordinate mice displayed significantly fewer pushing and advancing behaviors, and more retreat behaviors compared with dominant mice. Furthermore, subordinate mice had significantly more immobility durations in the TST, but significantly fewer distances, entries, and time into the center in the OFT, as well as significantly less percent of distances, entries, and time into the open arms in the EPMT, compared with dominant mice, which indicated that subordinate mice displayed depression- and anxiety-like behaviors. In addition, chronic restraint stress (CRS) significantly induced depression- and anxiety-like behaviors in mice and altered social dominance behaviors in the tube test. CRS mice displayed significantly fewer pushing and advancing behaviors, and more retreat behaviors compared with control mice. Furthermore, low social rank and CRS significantly decreased the firing of pyramidal neurons and γ-oscillation activity in the mPFC. Taken together, the present study revealed an inverse relationship between social hierarchy and depression/anxiety, and the neural basis underlying this association might be the excitability of pyramidal neurons and γ oscillation in the mPFC. These findings established an important foundation for a depression/anxiety model based on social hierarchy and provided a new avenue for the development of therapies for stress-related mood disorders.

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Appetite suppressive role of medial septal glutamatergic neurons.

Publications

Appetite suppressive role of medial septal glutamatergic neurons.

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