Ethanol modulation of cortico-basolateral amygdala circuits: Neurophysiology and behavior

Abstract

This review highlights literature relating the anatomy, physiology, and behavioral contributions by projections between rodent prefrontal cortical areas and the basolateral amygdala. These projections are robustly modulated by both environmental experience and exposure to drugs of abuse including ethanol. Recent literature relating optogenetic and chemogenetic dissection of these circuits within behavior both compliments and occasionally challenges roles defined by more traditional pharmacological or lesion-based approaches. In particular, cortico-amygdala circuits help control both aversive and reward-seeking. Exposure to pathology-producing environments or abused drugs dysregulates the relative 'balance' of these outcomes. Modern circuit-based approaches have also shown that overlapping populations of neurons within a given brain region frequently govern both aversion and reward-seeking. In addition, these circuits often dramatically influence 'local' cortical or basolateral amygdala excitatory or inhibitory circuits. Our understanding of these neurobiological processes, particularly in relation to ethanol research, has just begun and represents a significant opportunity. This article is part of the special Issue on 'Neurocircuitry Modulating Drug and Alcohol Abuse'.

Keywords: Abused drugs; Chemogenetics; Conditioned behavior; Optogenetics.

Figure 1.. Optogenetics- or chemogenetics-based dissection of cortico-basolateral amygdala circuits.

(A) Representative experimental design for circuit-based analysis of behavior. Microinjection of virally-encoded, light-gated opsins or designer receptors (not shown) into region “A” expresses these proteins within both local principal neurons and their downstream terminal fields (region “B”). Selective delivery of light or ligands into region “B” permits some understanding of the behavioral contributions by this A–B circuit. (B) The rat basolateral amygdala (BLA), including the lateral and basolateral subdivisions, is here represented in a coronal brain slice from the rat (left). The region contains of both glutamatergic principal neurons and local GABAergic interneurons that provide feed-back and feed-forward inhibition. Both glutamatergic and GABAergic BLA neurons receive excitatory input from frontal cortical areas.

Figure 2.. Summary of regions/projections discussed in the current review and effects of ethanol exposure on these synapses.

Projections are indicated by lines with known connections denoted by the arrowheads. Ethanol facilitation of projections onto basolateral amygdala principal neurons are indicated by green lines while inhibitory effects are noted by red lines. (→) indicates known effects on projections within reciprocal circuits. Black arrows indicate known projections with clearly established effects of ethanol within that particular prefrontal region, but unknown effect on the projection itself. Abbreviations: BLA – basolateral amygdala; PLC – prelimbic prefrontal cortex (section 2.1); ILC – infralimbic prefrontal cortex (section 2.2); rACC and cACC – rostral and caudal anterior cingulate cortex, respectively (section 2.3); lOFC & vOFC – lateral and ventral orbitofrontal cortex, respectively (section 3); aAIC – anterior agranular insular cortex (section 4).