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The hippocampus, particularly its ventral domain, can promote negative affective states (i.e. stress and anxiety) that play an integral role in the development and persistence of alcohol use disorder (AUD). The ventral hippocampus (vHC) receives strong excitatory input from the basolateral amygdala (BLA) and the BLA-vHC projection bidirectionally modulates anxiety-like behaviors. However, no studies have examined the effects of chronic alcohol on the BLA-vHC circuit. In the present study, we used ex vivo electrophysiology in conjunction with optogenetic approaches to examine the effects of chronic intermittent ethanol exposure (CIE), a well-established rodent model of AUD, on the BLA-vHC projection and putative intrinsic vHC synaptic plasticity. We discovered prominent BLA innervation in the subicular region of the vHC (vSub). CIE led to an overall increase in the excitatory/inhibitory balance, an increase in AMPA/NMDA ratios but no change in paired-pulse ratios, consistent with a postsynaptic increase in excitability in the BLA-vSub circuit. CIE treatment also led to an increase in intrinsic network excitability in the vSub. Overall, our findings suggest a hyperexcitable state in BLA-vSub specific inputs as well as intrinsic inputs to vSub pyramidal neurons which may contribute to the negative affective behaviors associated with CIE.

No abstract

Alcohol use disorder (AUD) and anxiety/stressor disorders frequently co‐occur and this dual diagnosis represents a major health and economic problem worldwide. The basolateral amygdala (BLA) is a key brain region that is known to contribute to the aetiology of both disorders. Although many studies have implicated BLA hyperexcitability in the pathogenesis of AUD and comorbid conditions, relatively little is known about the specific efferent projections from this brain region that contribute to these disorders. Recent optogenetic studies have shown that the BLA sends a strong monosynaptic excitatory projection to the ventral hippocampus (vHC) and that this circuit modulates anxiety‐ and fear‐related behaviours. However, it is not known if this pathway influences alcohol drinking‐related behaviours. Here, we employed a rodent operant self‐administration regimen that procedurally separates appetitive (e.g. seeking) and consummatory (e.g., drinking) behaviours, chemogenetics and brain region‐specific microinjections, to determine if BLA‐vHC circuitry influences alcohol and sucrose drinking‐related measures. We first confirmed prior optogenetic findings that silencing this circuit reduced anxiety‐like behaviours on the elevated plus maze. We then demonstrated that inhibiting the BLA‐vHC pathway significantly reduced appetitive drinking‐related behaviours for both alcohol and sucrose while having no effect on consummatory measures. Taken together, these findings provide the first indication that the BLA‐vHC circuit may regulate appetitive reward seeking directed at alcohol and natural rewards and add to a growing body of evidence suggesting that dysregulation of this pathway may contribute to the pathophysiology of AUD and anxiety/stressor‐related disorders.

No abstract