Cortical and amygdalar neuronal ensembles in alcohol seeking, drinking and withdrawal

Abstract

Alcohol induces many alterations in the brain that are thought to contribute to alcohol addiction. Most of the known alterations are induced in all neurons of a brain area or all neurons of a given cell type, regardless of whether they were activated during behavior. While these alterations can have important modulatory effects on behavior, they cannot explain why animals respond specifically to alcohol-paired cues as opposed to all other non-paired cues and evoke highly specific goal-directed learned responses in models of drug craving. As an alternative, we hypothesize another class of alterations that are induced only within sparsely distributed patterns of neurons, called neuronal ensembles, that are selectively activated by alcohol-specific cues during behavior and encode the long-term memories underlying these learned behaviors in animal models of alcohol addiction. Here we review recent studies and techniques used to identify the role of neuronal ensembles in animal models of different phases of the alcohol addiction cycle. This article is part of the Special Issue entitled "Alcoholism".

Keywords: Addiction; Alcoholism; CeA; Cell assembly; Daun02; Ethanol; Prefrontal; Reinstatement; Withdrawal.

Figure 1. Hypothetical framework

Activation of a small population of neurons in the IL by alcohol-related cues inhibits alcohol seeking hypothetically through inhibition of efferents to the Nucleus accumbens (NAC) and central nucleus of the amygdala (CeA). Activation of a small population of neurons in the CeA during withdrawal promotes alcohol drinking, hypothetically through activation of efferents to the bed nucleus of the stria terminalis (BNST), lateral hypothalamus (LH), substantia inominata (SI) and parabrachial nucleus (PBN). Blue dots represent non-activated neurons while green dots represent neurons activated by external (alcohol-related) and internal (withdrawal/abstinence-related) cues. Green arrows represent excitatory pathways while red arrows represent inhibitory pathways (possibly disynaptic).