Cell-type-specific manifold analysis discloses independent geometric transformations in the hippocampal spatial code

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Complex opioid driven modulation of glutamatergic and cholinergic neurotransmission in a GABAergic brain nucleus associated with emotion, reward and addiction

Published: March 31, 2025

The medial habenula (mHb)/interpeduncular nucleus (IPN) circuitry is resident to divergent molecular, neurochemical and cellular components which, in concert, perform computations drive emotion, reward addiction behaviors. Although housing one of the most prominent mu opioid receptor (mOR) expression levels brain, remarkably little known as how they impact mHb/IPN circuit function at granular level. In this study, our systematic functional pharmacogenetic analyses demonstrate that mOR activation attenuates glutamatergic signaling whilst producing an opposing potentiation glutamatergic/cholinergic co-transmission mediated by mHb substance P cholinergic neurons, respectively. Intriguingly, latter non-canonical augmentation developmentally regulated only emerging during later postnatal stages. Further, specific potassium channels act a molecular brake on nicotinic IPN with arm neurotransmission being operational following attenuation Kv1 function. Thus, mORs play complex role controlling salience distinct afferent inputs transmitter modalities ultimately influences synaptic recruitment common downstream GABAergic neurons. Together, these observations provide framework for future investigations aimed identifying neural underpinnings maladaptive behaviors can emerge when endogenous or exogenous opioids, including potent synthetic analogs such fentanyl, modulate/hijack vulnerable stages adolescence adulthood.

Language: Английский

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Complex opioid driven modulation of glutamatergic and cholinergic neurotransmission in a GABAergic brain nucleus associated with emotion, reward and addiction

Published: March 31, 2025

The medial habenula (mHb)/interpeduncular nucleus (IPN) circuitry is resident to divergent molecular, neurochemical and cellular components which, in concert, perform computations drive emotion, reward addiction behaviors. Although housing one of the most prominent mu opioid receptor (mOR) expression levels brain, remarkably little known as how they impact mHb/IPN circuit function at granular level. In this study, our systematic functional pharmacogenetic analyses demonstrate that mOR activation attenuates glutamatergic signaling whilst producing an opposing potentiation glutamatergic/cholinergic co-transmission mediated by mHb substance P cholinergic neurons, respectively. Intriguingly, latter non-canonical augmentation developmentally regulated only emerging during later postnatal stages. Further, specific potassium channels act a molecular brake on nicotinic IPN with arm neurotransmission being operational following attenuation Kv1 function. Thus, mORs play complex role controlling salience distinct afferent inputs transmitter modalities ultimately influences synaptic recruitment common downstream GABAergic neurons. Together, these observations provide framework for future investigations aimed identifying neural underpinnings maladaptive behaviors can emerge when endogenous or exogenous opioids, including potent synthetic analogs such fentanyl, modulate/hijack vulnerable stages adolescence adulthood.

Language: Английский

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Input-output specific orchestration of aversive valence in lateral habenula during stress dynamics

Journal of Zhejiang University SCIENCE B, Journal Year: 2024, Volume and Issue: unknown

Published: April 3, 2024

Language: Английский

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System-level time computation and representation in the suprachiasmatic nucleus revealed by large-scale calcium imaging and machine learning

Cell Research, Journal Year: 2024, Volume and Issue: 34(7), P. 493 - 503

Published: April 11, 2024

The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of day remains enigmatic. Here we show that population-level Ca

Language: Английский

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