Biology subjects

Choleris, E.

Publications and source records attributed to Choleris, E..

3 recordsLinked to original sources

bioRxiv2026

Estrogen receptor alpha regulates alcohol craving in females: convergent evidence from mouse models and human genetics

Alcohol craving and consumption fluctuate across the reproductive cycle in females with alcohol use disorder (AUD), suggesting that estrogen signaling contributes to disease vulnerability. Here, we investigated the role of estrogen receptor alpha (ER; Esr1; ESR1) in alcohol seeking using complementary mouse and human approaches, as this receptor was previously identified as a risk factor for AUD. Female mice were characterized in an IntelliCage-based multidimensional AUD paradigm that stratifies individuals into AUD-prone and AUD-resistant phenotypes. Transcriptomic profiling of the amygdala revealed that Esr1 is a top transcription factor for differentially expressed genes in mice drinking alcohol, and the estrogen signaling pathway was deregulated specifically in AUD-prone mice. Although alcohol exposure did not alter overall Esr1/ER mRNA or protein abundance, both transcript and protein levels positively correlated with cue-induced alcohol seeking, indicating that inter-individual variation in ER signaling predicts relapse-like behavior. Causal manipulations confirmed a functional role of ER. Local knockdown of Esr1 in the basolateral amygdala reduced excitatory synaptic transmission, attenuated alcohol motivation, cue-induced seeking, and relapse drinking, and impaired cue-associated memory recall without affecting anxiety-like behavior. Similarly, ovariectomy decreased amygdala ER expression, altered synaptic protein markers, and reduced alcohol-seeking behaviors, supporting regulation by endogenous ovarian hormones. Extending these findings to humans, ESR1 gene polymorphisms (rs6902771, rs11155819 and rs6557171) were associated with the probability of alcohol binge drinking and alcohol consumption days as well as craving and loss of control in real world in a longitudinal clinical cohort, while ESR1 mRNA blood levels were increased in women with AUD diagnosis. Together, these convergent molecular, circuit, behavioral, and genetic data identify ER signaling in the amygdala as an important modulator of alcohol-seeking behavior induced by alcohol cue and relapse vulnerability, highlighting estrogen pathways as potential therapeutic targets and markers for AUD.

neuroscience↗

bioRxiv2023

Prefrontal layer V pyramidal neurons comprise multiple subtypes with distinct nicotinic responses and projection targets

The neurotransmitter acetylcholine supports goal-directed cognitive functions via activation of its nicotinic and muscarinic classes of receptors within the prefrontal cortex. These receptors are expressed on pyramidal neurons located within layer V of the prefrontal cortex, which integrate afferent signals and contribute toward cognitive circuits via efferent projections to cortical and subcortical targets. Using whole-cell electrophysiology, retrograde labelling, and neuron reconstruction in the juvenile mouse prefrontal cortex, we identified three unique isoform-specific nicotinic receptor responses that are present in distinct subtypes of layer V pyramidal neurons. Broadly, we observed 7 or 7/{beta}2* nicotinic responses in burst-firing neurons that project to the contralateral cortex or nucleus accumbens, respectively, and {beta}2* nicotinic responses in regular-firing neurons that project to the ventromedial thalamus. These findings provide insight into a receptor isoform-specific mechanism by which nicotinic acetylcholine neurotransmission may support cognitive functions via modulation of distinct efferent projections from this brain region.

neuroscience↗

bioRxiv2022

Social memory in female mice is rapidly modulated by 17β-estradiol through ERK and Akt modulation of synapse formation

BackgroundSocial memory is essential to the functioning of a social animal within a group. Estrogens can affect social memory too quickly for classical genomic mechanisms. Previously, 17{beta}-estradiol (E2) rapidly facilitated short-term social memory and increased nascent synapse formation, these synapses being potentiated following neuronal activity. However, what mechanisms underlie and co-ordinate the rapid facilitation of social memory and synaptogenesis are unclear. Here, the necessity of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) signaling for rapid facilitation of short-term social memory and synaptogenesis was tested. MethodsMice performed a short-term social memory task or were used as task-naive controls. ERK and PI3K pathway inhibitors were infused intra-dorsal hippocampally 5 minutes before E2 infusion. Forty minutes following intrahippocampal E2 or vehicle administration, tissues were collected for quantification of glutamatergic synapse number in the CA1. ResultsDorsal hippocampal E2 rapid facilitation of short-term social memory depended upon ERK and PI3K pathways. E2 increased glutamatergic synapse number (GluA1/bassoon colocalization) in task-performing mice but decreased synapse number in task-naive mice. Critically, ERK signaling was required for synapse formation/elimination in task-performing and task-naive mice, whereas PI3K inhibition blocked synapse formation only in task-performing mice. ConclusionsWhilst ERK and PI3K are both required for E2 facilitation of short-term social memory and synapse formation, only ERK is required for synapse elimination. This demonstrates previously unknown, bidirectional, rapid actions of E2 on brain and behaviour and underscores the importance of estrogen signaling in the brain to social behaviour.

neuroscience↗