Lack of Belonging Predicts Depressive Symptomatology in College Students.

Feeling a sense of belonging is a central human motivation that has consequences for mental health and well-being, yet surprisingly little research has examined how belonging shapes mental health among young adults. In three data sets from two universities (exploratory study: N = 157; Confirmatory Study 1: N = 121; Confirmatory Study 2: n = 188 in winter term, n = 172 in spring term), we found that lower levels of daily-assessed feelings of belonging early and across the academic term predicted higher depressive symptoms at the end of the term. Furthermore, these relationships held when models controlled for baseline depressive symptoms, sense of social fit, and other social factors (loneliness and frequency of social interactions). These results highlight the relationship between feelings of belonging and depressive symptoms over and above other social factors. This work underscores the importance of daily-assessed feelings of belonging in predicting subsequent depressive symptoms and has implications for early detection and mental health interventions among young adults.

Optogenetic studies of nicotinic contributions to cholinergic signaling in the central nervous system.

Molecular manipulations and targeted pharmacological studies provide a compelling picture of which nicotinic receptor subtypes are where in the central nervous system (CNS) and what happens if one activates or deletes them. However, understanding the physiological contribution of nicotinic receptors to endogenous acetylcholine (ACh) signaling in the CNS has proven a more difficult problem to solve. In this review, we provide a synopsis of the literature on the use of optogenetic approaches to control the excitability of cholinergic neurons and to examine the role of CNS nicotinic ACh receptors (nAChRs). As is often the case, this relatively new technology has answered some questions and raised others. Overall, we believe that optogenetic manipulation of cholinergic excitability in combination with some rigorous pharmacology will ultimately advance our understanding of the many functions of nAChRs in the brain.

Vigor Encoding in the Ventral Pallidum.

The ventral pallidum (VP) is the major downstream nucleus of the nucleus accumbens (NAc). Both VP and NAc neurons are responsive to reward-predictive stimuli and are critical drivers of reward-seeking behavior. The cue-evoked excitations and inhibitions of NAc neurons predict the vigor (latency and speed) of the cue-elicited locomotor approach response and encode the animal's proximity to the movement target, but do not encode more specific movement features such as turn direction. VP neurons also encode certain vigor parameters, but it remains unknown whether they also encode more specific movement features, and whether such encoding could account for vigor encoding. To address these questions, we recorded the firing of neurons in the VP of freely moving male rats performing a discriminative stimulus (DS) task. Similar to NAc neurons, VP neurons' cue-evoked excitations were correlated with the speed of the upcoming approach movement and the animal's proximity to the movement target at cue onset. Unlike NAc neurons, VP neurons' firing reflected the efficiency of the approach movement path but not the latency to initiate locomotion. VP cue-evoked excitations are unlikely to be directly influenced by NAc cue-evoked excitations because unilateral treatment of the NAc with a dopamine D1 receptor antagonist, a manipulation that reduces NAc neurons' cue-evoked excitations, did not alter ipsilateral VP cue-evoked excitations. These observations suggest that the two structures receive simultaneous activation by inputs conveying similar but not identical information, and work in parallel to set the vigor of the behavioral response.

Cholinergic Signaling Controls Conditioned Fear Behaviors and Enhances Plasticity of Cortical-Amygdala Circuits.

We examined the contribution of endogenous cholinergic signaling to the acquisition and extinction of fear- related memory by optogenetic regulation of cholinergic input to the basal lateral amygdala (BLA). Stimulation of cholinergic terminal fields within the BLA in awake-behaving mice during training in a cued fear-conditioning paradigm slowed the extinction of learned fear as assayed by multi-day retention of extinction learning. Inhibition of cholinergic activity during training reduced the acquisition of learned fear behaviors. Circuit mechanisms underlying the behavioral effects of cholinergic signaling in the BLA were assessed by in vivo and ex vivo electrophysiological recording. Photostimulation of endogenous cholinergic input (1) enhances firing of putative BLA principal neurons through activation of acetylcholine receptors (AChRs), (2) enhances glutamatergic synaptic transmission in the BLA, and (3) induces LTP of cortical-amygdala circuits. These studies support an essential role of cholinergic modulation of BLA circuits in the inscription and retention of fear memories.