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Your search keyword '"Malini Suresh Nair"' showing total 4 results
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4 results on '"Malini Suresh Nair"'

1. Somatostatin neurons in the bed nucleus of the stria terminalis play a sex-dependent role in binge Drinking

Author

Malini Suresh Nair, Nigel C. Dao, Daniela Lopez Melean, Keith R. Griffith, W. David Starnes, J. Brody Moyer, Avery R. Sicher, Dakota F. Brockway, Kathleen D. Meeks, and Nicole A. Crowley

Subjects
Alcohol, Peptide, Somatostatin, Bed nucleus of the stria terminalis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Alcohol use disorder (AUD) is characterized by alcohol use coupled with chronic relapse and involves brain regions including the bed nucleus of the stria terminalis (BNST). Here, we explore whether a subpopulation of BNST neurons, somatostatin (SST) expressing GABAergic neurons, play a role in an animal model of binge-like alcohol consumption, the Drinking in the Dark (DID) model. Chemogenetic activation of BNST SST neurons reduced binge alcohol consumption in female but not male SST-Cre mice, while inhibition of these neurons in the same mice had no effect. In addition, chemogenetic activation of these neurons did not cause apparent changes in models of anxiety-like behavior in either sex. Basal SST cell counts and intrinsic excitability of SST neurons were compared to attempt to understand sex differences in DREADD-induced changes in drinking, and while males had a greater number of BNST SST neurons, this effect went away when normalizing for total BNST volume. Together, these results suggest SST neurons in the BNST should be further explored as a potential neuronal subtype modulated by AUD, and for their therapeutic potential.

Published
2022
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2. Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions

Author

Nigel C. Dao, Malini Suresh Nair, Sarah N. Magee, J. Brody Moyer, Veronica Sendao, Dakota F. Brockway, and Nicole A. Crowley

Subjects
forced abstinence, alcohol, sex, stress, somatostatin, prefrontal cortex, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Forced abstinence (FA) from alcohol has been shown to produce a variety of anxiety- and depression-like symptoms in animal models. Somatostatin (SST) neurons, a subtype of GABAergic neurons found throughout the brain, are a novel neural target with potential treatment implications in affective disorders, yet their role in alcohol use disorders (AUD) remains to be explored. Here, we examined the neuroadaptations of SST neurons during forced abstinence from voluntary alcohol consumption. Following 6 weeks of two-bottle choice alcohol consumption and protracted forced abstinence, male and female C57BL/6J mice exhibited a heightened, but sex-specific, depressive-like behavioral profile in the sucrose preference test (SPT) and forced swim test (FST), without changes in anxiety-like behaviors in the elevated plus maze (EPM) and open field test (OFT). FST-induced cFos expressions in the prefrontal cortex (PFC) and ventral bed nucleus of the stria terminalis (vBNST) were altered in FA-exposed female mice only, suggesting a sex-specific effect of forced abstinence on the neural response to acute stress. SST immunoreactivity in these regions was unaffected by forced abstinence, while differences were seen in SST/cFos co-expression in the vBNST. No differences in cFos or SST immunoreactivity were seen in the lateral central nucleus of the amygdala (CEA) and the basolateral amygdala (BLA). Additionally, SST neurons in female mice displayed opposing alterations in the PFC and vBNST, with heightened intrinsic excitability in the PFC and diminished intrinsic excitability in the vBNST. These findings provide an overall framework of forced abstinence-induced neuroadaptations in these key brain regions involved in emotional regulation and processing.

Published
2020
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3. Somatostatin neurons control an alcohol binge drinking prelimbic microcircuit in mice

Author

Dakota F. Brockway, Nicole A. Crowley, Avery R. Sicher, Malini Suresh Nair, and Nigel C. Dao

Subjects
Pharmacology, Chemistry, Alcohol use disorder, Inhibitory postsynaptic potential, medicine.disease, Cortex (botany), Psychiatry and Mental health, Somatostatin, nervous system, Cellular neuroscience, Excitatory postsynaptic potential, medicine, GABAergic, Hypoactivity, Neuroscience
Abstract

Somatostatin (SST) neurons have been implicated in a variety of neuropsychiatric disorders such as depression and anxiety, but their role in substance use disorders, including alcohol use disorder (AUD), is not fully characterized. Here, we found that repeated cycles of alcohol binge drinking via the Drinking-in-the-Dark (DID) model led to hypoactivity of SST neurons in the prelimbic (PL) cortex by diminishing their action potential firing capacity and excitatory/inhibitory transmission dynamic. We examined their role in regulating alcohol consumption via bidirectional chemogenetic manipulation. Both hM3Dq-induced excitation and KORD-induced silencing of PL SST neurons reduced alcohol binge drinking in males and females, with no effect on sucrose consumption. Alcohol binge drinking disinhibited pyramidal neurons by augmenting SST neurons-mediated GABA release and synaptic strength onto other GABAergic populations and reducing spontaneous inhibitory transmission onto pyramidal neurons. Pyramidal neurons additionally displayed increased intrinsic excitability. Direct inhibition of PL pyramidal neurons via hM4Di was sufficient to reduce alcohol binge drinking. Together these data revealed an SST-mediated microcircuit in the PL that modulates the inhibitory dynamics of pyramidal neurons, a major source of output to subcortical targets to drive reward-seeking behaviors and emotional response.

Published
2021

4. Bi-directional control of a prelimbic somatostatin microcircuit decreases binge alcohol consumption

Author

Dakota F. Brockway, Malini Suresh Nair, Nikki Crowley, and Nigel C. Dao

Subjects
endocrine system, Chemistry, Binge drinking, Alcohol use disorder, medicine.disease, Inhibitory postsynaptic potential, Synapse, Somatostatin, nervous system, Excitatory postsynaptic potential, medicine, GABAergic, Hypoactivity, Neuroscience
Abstract

Somatostatin neurons have been implicated in a variety of neuropsychiatric disorders such as depression and anxiety, but their role in substance abuse disorders, including alcohol use disorder (AUD), is not fully characterized. Here we found that repeat cycles of alcohol binge drinking in the Drinking-in-the-Dark (DID) model led to hypoactivity of somatostatin (SST) neuronal in the prelimbic (PL) cortex by diminishing their action potential firing capacity and excitatory/inhibitory transmission dynamic. We examined their role in regulating alcohol consumption via bidirectional chemogenetic manipulation. Both hM3Dq-induced excitation and KORD-induced silencing of PL SST neurons paradoxically reduced alcohol binge drinking in males and females, with no effect on sucrose consumption. This effect is mediated directly via monosynaptic connection from SST neurons onto pyramidal neurons and indirectly via an intermediate GABAergic source. Optogenetic-assisted circuit mapping revealed that PL SST neurons preferentially synapse onto pyramidal neurons over other GABAergic populations in males, whereas SST neuron-mediated inhibition is balanced across cell types in females. Alcohol binge drinking disinhibits pyramidal neurons by augmenting SST neurons-mediated GABA release and synaptic strength onto other GABAergic populations. Together these data suggest substantial interaction between alcohol binge drinking and SST neurons inhibitory circuit in the PL, as well as provide evidence for these neurons as a potential therapeutic candidate for the treatment of alcohol use disorders, including binge drinking.

Published
2020

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