Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1

Robert, Valérie; Therreau, Ludivine; Chevaleyre, Vivien; Lepicard, Eude; Cognet, Julie; Huang, Arthur; Boehringer, Roman; Polygalov, Denis; McHugh, Thomas J.; Piskorowski, Rebecca A.

doi:10.7554/elife.63352

Cited by 34 publications

(19 citation statements)

References 97 publications

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“…We tested whether depolarization of CA2 pyramidal neurons could induce LTP at SuM-CA2 pyramidal neuron synapses. In agreement with recent reports ( 13 , 41 ), light activation of the SuM fibers evoked oEPSCs recorded from CA2 pyramidal neurons (19.4 ± 3.4 pA, n = 10) ( Fig. 3 E and F ).…”

Section: Resultssupporting

confidence: 93%

Excitatory selective LTP of supramammillary glutamatergic/GABAergic cotransmission potentiates dentate granule cell firing

Tabuchi

Sakaba

Hashimotodani

2022

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

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Significance It is now established that many neurons can release multiple transmitters. Recent studies revealed that fast-acting neurotransmitters, glutamate and GABA, are coreleased from the same presynaptic terminals in some adult brain regions. The dentate gyrus (DG) granule cells (GCs) are innervated by the hypothalamic supramammillary nucleus (SuM) afferents that corelease glutamate and GABA. However, how these functionally opposing neurotransmitters contribute to DG information processing remains unclear. We show that glutamatergic, but not GABAergic, cotransmission exhibits long-term potentiation (LTP) at SuM-GC synapses. By the excitatory selective LTP, the excitation/inhibition balance of SuM inputs increases, and GC firing is enhanced. This study provides evidence that glutamatergic/GABAergic cotransmission balance is rapidly changed in an activity-dependent manner, and such plasticity may modulate DG activity.

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Section: Resultssupporting

confidence: 93%

Excitatory selective LTP of supramammillary glutamatergic/GABAergic cotransmission potentiates dentate granule cell firing

Tabuchi

Sakaba

Hashimotodani

2022

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

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“…For the rest of this study, we performed whole-cell recordings from visually identified tdTomato + cells in the central CA2 ( Dudek et al, 2016 ), using both male and female adult animals. Characterization of intrinsic membrane properties was also performed at the beginning of each recording for further validation of typical CA2 PYR features by electrophysiological criteria ( Chevaleyre and Siegelbaum, 2010 ; Hitti and Siegelbaum, 2014 ; Tirko et al, 2018 ; Robert et al, 2020 , 2021 ). Alexa Fluor 633 dye was included in the internal solution for some recordings when post hoc recognition was needed ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Oxytocin-modulated ion channel ensemble controls depolarization, integration and burst firing in CA2 pyramidal neurons

et al. 2022

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Oxytocin (OXT) and OXT receptor (OXTR)-mediated signaling control excitability, firing patterns, and plasticity of hippocampal CA2 pyramidal neurons, which are pivotal in generation of brain oscillations and social memory. Nonetheless, the ionic mechanisms underlying OXTR-induced effects in CA2 neurons are not fully understood. Using slice physiology in a reporter mouse line and interleaved current-clamp and voltage-clamp experiments, we systematically identified the ion channels modulated by OXT signaling in CA2 pyramidal cells (PYRs) in mice of both sexes and explored how changes in channel conductance support altered electrical activity. Activation of OXTRs inhibits an outward potassium current mediated by inward rectifier potassium channels ( I Kir ) and thus favoring membrane depolarization. Concomitantly, OXT signaling also diminishes inward current mediated by hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels ( I h ), providing a hyperpolarizing drive. The combined reduction in both I Kir and I h synergistically elevate the membrane resistance and favor dendritic integration while the membrane potential is restrained from quickly depolarizing from rest. As a result, the responsiveness of CA2 PYRs to synaptic inputs is highly sharpened during OXTR activation. Unexpectedly, OXTR signaling also strongly enhances a tetrodotoxin-resistant (TTX-R), voltage-gated sodium current that helps drive the membrane potential to spike threshold and thus promote rhythmic firing. This novel array of OXTR-stimulated ionic mechanisms operates in close coordination and underpins OXT-induced burst firing, a key step in CA2 PYRs' contribution to hippocampal information processing and broader influence on brain circuitry. Our study deepens our understanding of underpinnings of OXT-promoted social memory and general neuropeptidergic control of cognitive states. SIGNIFICANCE STATEMENT Oxytocin (OXT) plays key roles in reproduction, parenting and social and emotional behavior, and deficiency in OXT receptor (OXTR) signaling may contribute to neuropsychiatric disorders. We identified a novel array of OXTR-modulated ion channels that operate in close coordination to retune hippocampal CA2 pyramidal neurons, enhancing responsiveness to synaptic inputs and sculpting output. OXTR signaling inhibits both potassium conductance ( I Kir ) and mixed cation conductance ( I h ), engaging opposing influences on membrane potential, stabilizing it while synergistically elevating membrane resistance and electrotonic spread. OXT signaling also facilitates a tetrodotoxin-resistant (TTX-R) Na + current, not previously described in hippocampus (HP), engaged on further depolarization. This TTX-R current lowers the spike threshold and supports rhythmic depolarization and bu...

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“…SuM neurons have been shown to project to the hippocampus, specifically the hippocampal CA2 in mice 31,49 . Here, we set to confirm if SuM⍰CA2 projections also exist in rats and to determine if OXTRs are specifically expressed in these projecting neurons.…”

Section: Resultsmentioning

confidence: 99%

Oxytocin Activity in the Paraventricular and Supramammillary Nuclei of the Hypothalamus is Essential for Social Recognition Memory in Rats

Rajamani

Barbier

Lefèvre

et al. 2022

Preprint

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Oxytocin plays an important role in modulating social recognition memory. However, the direct implication of oxytocin neurons of the paraventricular nucleus of the hypothalamus (PVH) and their downstream hypothalamic targets in regulating the short- and long-term forms of social recognition memory is not fully understood. In this study, we employed a chemogenetic approach to specifically target the activity of PVH oxytocin neurons in rats and found that silencing these neurons impaired both long and short-term social recognition memory. We combined viral mediated fluorescent labeling of oxytocin neurons with immunohistochemical techniques and identified the supramammillary nucleus (SuM) of the hypothalamus, as a novel target of PVH oxytocinergic axonal projections. Furthermore, we used multiplex fluorescence in-situ hybridization and found that oxytocin receptors in the SuM are predominantly in excitatory neurons. Finally, we examined the role of the SuM in social recognition memory, by using a highly selective antagonist to block oxytocin receptors in the SuM. We found that oxytocin activity in the SuM is necessary for the formation of long- and short-term social recognition memory. This study discovered a previously undescribed role for the SuM in regulating social recognition memory via oxytocin signaling and reinforces the specific role of PVH oxytocin neurons in regulating social recognition memory.

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Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1

Cited by 34 publications

References 97 publications

Excitatory selective LTP of supramammillary glutamatergic/GABAergic cotransmission potentiates dentate granule cell firing

Excitatory selective LTP of supramammillary glutamatergic/GABAergic cotransmission potentiates dentate granule cell firing

Oxytocin-modulated ion channel ensemble controls depolarization, integration and burst firing in CA2 pyramidal neurons

Oxytocin Activity in the Paraventricular and Supramammillary Nuclei of the Hypothalamus is Essential for Social Recognition Memory in Rats

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