Acquisition and extinction of learned fear responses utilize conserved but flexible neural circuits. Here we show that acquisition of conditioned freezing behavior is associated with dynamic remodeling of relative excitatory drive from the basolateral amygdala (BLA) away from corticotropin releasing factor-expressing (CRF+) central lateral amygdala (CeL) neurons, and toward non-CRF+ (CRF−) and somatostatin-expressing (SOM+) neurons, while fear extinction training remodels this circuit back toward favoring CRF+ neurons. Importantly, BLA activity is required for this experience-dependent remodeling, while directed inhibition of the BLA-CeL circuit impairs both fear memory acquisition and extinction memory retrieval. Additionally, ectopic excitation of CRF+ neurons impairs memory acquisition and facilities extinction, whereas CRF+ neuron inhibition impairs extinction memory retrieval, supporting the notion that CRF+ neurons serve to inhibit learned freezing behavior. These data suggest afferent-specific dynamic Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Circadian photoperiod, or day length, changes with the seasons and influences behavior to allow animals to adapt to their environment. Photoperiod is also associated with seasonal rhythms of affective state, as evidenced by seasonality of several neuropsychiatric disorders. Interestingly, seasonality tends to be more prevalent in women for affective disorders such as Major Depressive Disorder and Bipolar Disorder. However, the underlying neurobiological processes contributing to sex-linked seasonality of affective behaviors are largely unknown. Mesolimbic dopamine input to the nucleus accumbens (NAc) contributes to the regulation of affective state and behaviors. Additionally, sex differences in the mesolimbic dopamine pathway are well-established. Therefore, we hypothesize that photoperiod may drive differential modulation of NAc dopamine in males and females. Here, we used fast-scan cyclic-voltammetry (FSCV) to explore whether photoperiod can modulate sub-second dopamine signaling dynamics in the NAc core of male and female mice raised in seasonally relevant photoperiods. We found that photoperiod modulates dopamine signaling in the NAc core, and that this effect is sex-specific to females. Both release and uptake of dopamine were enhanced in the NAc core of female mice raised in long, summer-like photoperiods, whereas we did not find photoperiodic effects on NAc core dopamine in males. These findings uncover a potential neural circuit basis for sex-linked seasonality in affective behaviors.Significance StatementDay length, or photoperiod, is a reliable indicator of the changing seasons, and is a powerful environmental cue influencing affective state and behavior. While studies have shown that photoperiod can modulate neurotransmitter systems involved in affective behavior, like the dopamine system, there are few studies examining effects of photoperiod on the synaptic level. Here we assess mesolimbic dopamine dynamics in mice maintained in seasonal photoperiods. We found a sex-specific effect wherein photoperiod modulates dopamine release from and uptake in dopaminergic terminals in the nucleus accumbens core of female mice with long summer-like photoperiods increasing dopamine release, thus uncovering a potential synaptic basis for sex-linked seasonality in affective behaviors.

No abstract

Stress disorders, depression, anxiety, and substance use disorder, are regulated by serotonin (5HT). The dorsal raphe nucleus (DRN), the major site for neuronal 5HT synthesis, sends projections to the nucleus accumbens (NAc). NAc glutamatergic synapse adaptations are consistent with changes in mood and reward, key components of stress disorders. A subpopulation of DRN projection neurons express the β3 subunit of the integrin αvβ3 receptor. The integrin αvβ3 receptor regulates extracellular 5HT concentration by modulation of 5HT transporters. Previous work has implicated this cell adhesion receptor in modulating stress, as mice lacking the β3 subunit have increased vulnerability to chronic stress. However, how NAc function is regulated by the DRN β3 subunit and contributes to maladaptive reward behaviors as seen in stress disorders is unknown.Because the β3 subunit of the integrin avβ3 receptor is only expressed in a subpopulation of 5HT neurons, this suggests that it confers a specific function to this neuronal population. Using a mouse line with selective deletion of the β3 subunit within 5HT neurons, we are able to characterize its role in 5HT synaptic transmission. Using acute brain slice whole‐cell patch‐clamp electrophysiology, we characterize how the β3 subunit of 5HT inputs contribute to glutamatergic NAc synaptic transmission. Our data suggests that selective deletion of the β3 subunit in 5HT neurons blunts excitatory synaptic strength in the NAc. This suggests that the β3 subunit in 5HT neurons modulates excitatory input to the NAc, which may relate to stress response.Support or Funding InformationNIH T32 5T32MH064913‐15This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.