Effects of chronic ethanol exposure on dorsal medial striatal neurons receiving convergent inputs from the orbitofrontal cortex and basolateral amygdala.

Alcohol use disorder is associated with altered function of cortical-amygdala-striatal circuits such as the orbitofrontal cortex (OFC), basolateral amygdala (BLA) and their connections to the dorsal medial striatum (DMS) shown to be involved in goal-directed actions. Using retrobead tracing, we previously reported enhanced excitability of DMS-projecting OFC neurons in mice following 3-to-7-day withdrawal from chronic intermittent ethanol (CIE) exposure. In the same animals, spiking of DMS-projecting BLA neurons was decreased at 3-days post-withdrawal followed by an increase in firing at 7- and 14-days.

Chronic intermittent ethanol exposure differentially alters the excitability of neurons in the orbitofrontal cortex and basolateral amygdala that project to the dorsal striatum.

Alcohol use disorder is associated with altered neuron function including those in orbitofrontal cortex (OFC) and basolateral amygdala (BLA) that send glutamatergic inputs to areas of the dorsal striatum (DS) that mediate goal and habit directed actions. Previous studies reported that chronic intermittent (CIE) exposure to ethanol alters the electrophysiological properties of OFC and BLA neurons, although projection targets for these neurons were not identified. In this study, we used male and female mice and recorded current-evoked spiking of retrobead labeled DS-projecting OFC and BLA neurons in the same animals following air or CIE treatment.

The ethanol inhibition of basolateral amygdala neuron spiking is mediated by a γ-aminobutyric acid type A-mediated tonic current.

Background: The basolateral nucleus of the amygdala (BLA) plays an important role in the development of fear and anxiety-related behaviors. The BLA receives inputs from all sensory stimuli. After processing those stimuli, BLA neurons signal neurons within the central amygdala and other brain regions, including the ventral and dorsal striatum and frontal cortex.

Ethanol inhibition of lateral orbitofrontal cortex neuron excitability is mediated via dopamine D1/D5 receptor-induced release of astrocytic glycine.

Recent findings from this laboratory demonstrate that ethanol reduces the intrinsic excitability of orbitofrontal cortex (OFC) neurons via activation of strychnine-sensitive glycine receptors. Although the mechanism linking ethanol to the release of glycine is currently unknown, astrocytes are a source of neurotransmitters including glycine and activation of dopamine D1-like receptors has been reported to enhance extracellular levels of glycine via a functional reversal of the astrocytic glycine transporter GlyT1. We recently reported that like ethanol, dopamine or a D1/D5 receptor agonist increases a tonic current in lateral OFC (lOFC) neurons.

Distinct Region- and Time-Dependent Functional Cortical Adaptations in C57BL/6J Mice after Short and Prolonged Alcohol Drinking.

Alcohol (ethanol) use disorder is associated with changes in frontal cortical areas including the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) that contribute to cognitive deficits, uncontrolled drinking, and relapse. Acute ethanol exposure reduces intrinsic excitability of lateral OFC (lOFC) neurons, while chronic exposure and long-term drinking influence plasticity of intrinsic excitability and function of glutamatergic synapses. However, the time course that these adaptations occur across a history of ethanol drinking is unknown.