Decision making often requires weighing costs and benefits of different options that vary in terms of reward magnitude and uncertainty. Previous studies using pharmacological inactivations have shown that the basolateral amygdala (BLA) to nucleus accumbens (NAc) pathway promotes choice towards larger/riskier rewards. Neural activity in BLA and NAc shows distinct, phasic changes in firing prior to choice and following action outcomes, yet, how these temporally-discrete patterns of activity within BLA→NAc circuitry influence choice is unclear. We assessed how optogenetic silencing of BLA terminals in the NAc altered action selection during probabilistic decision making. Rats received intra-BLA infusions of viruses encoding the inhibitory opsin eArchT and were well trained on a probabilistic discounting task, where they chose between smaller/certain rewards and larger rewards delivered in a probabilistic manner, with the odds of obtaining the larger reward changing over a session (50–12.5%). During testing, activity of BLA→NAc inputs were suppressed with 4- to 7-s pulses of light delivered via optic fibers into the NAc during discrete task events: prior to choice or after choice outcomes. Inhibition prior to choice reduced selection of the preferred option, suggesting that during deliberation, BLA→NAc activity biases choice towards preferred rewards. Inhibition during reward omissions increased risky choice during the low-probability block, indicating that activity after non-rewarded actions serves to modify subsequent choice. In contrast, silencing during rewarded outcomes did not reliably affect choice. These data demonstrate how patterns of activity in BLA→NAc circuitry convey different types of information that guide action selection in situations involving reward uncertainty.

Emergent evidence demonstrates that excessive consumption of high fat and high sugar (HFHS) diets has negative consequences on hippocampal and prefrontal cortex (PFC) function. Moreover, the delayed maturation of the PFC including the late development of parvalbumin-expressing (PV) interneurons and perineuronal nets (PNNs) may promote vulnerability to HFHS diet-induced nutritional stress. However, the young brain may have some resistance to diet-induced neuroinflammation. Thus, we examined the impact of a HFHS diet commencing either in adolescence or adulthood in male mice. PV interneurons, PNNs and microglia were assessed using immunohistochemistry. We observed greater numbers of PV neurons and PNNs in the hippocampus and the prelimbic and infralimbic PFC in adult mice in comparison to our younger cohort. Mice that consumed HFHS diet as adults had reduced numbers of hippocampal PV neurons and PNNs, which correlated with adiposity. However, we saw no effects of diet on PV and PNNs in the PFC. HFHS diet increased microgliosis in the adult cohort, and morphological changes to microglia were observed in the PFC and hippocampus of the adolescent cohort, with a shift to activated microglia phenotypes. Taken together, these findings demonstrate different regional and age-specific effects of obesogenic diets on PV neurons, PNNs and microglia.

The ability to learn Pavlovian associations from environmental cues predicting positive outcomes is critical for survival, motivating adaptive behaviours. This cued-motivated behaviour depends on the nucleus accumbens (NAc). NAc output activity mediated by spiny projecting neurons (SPNs) is regulated by dopamine, but also by cholinergic interneurons (CINs), which can release acetylcholine and glutamate via the activity of the vesicular acetylcholine transporter (VAChT) or the vesicular glutamate transporter (VGLUT3), respectively. Here we investigated behavioural and neurochemical changes in mice performing a touchscreen Pavlovian approach task by recording dopamine, acetylcholine, and calcium dynamics from D1- and D2-SPNs using fibre photometry in control, VAChT or VGLUT3 mutant mice to understand how these signals cooperate in the service of approach behaviours toward reward-predicting cues. We reveal that NAc acetylcholine-dopaminergic signalling is continuously updated to regulate striatal output underlying the acquisition of Pavlovian approach learning toward reward-predicting cues.

Adult hippocampal neurogenesis is implicated in a number of disorders where reward processes are disrupted but whether new neurons regulate specific reward behaviors remains unknown. We find that blocking neurogenesis in rats reduces activation of the ventral dentate gyrus and causes a profound aversion for delayed rewards. Delay-based decision-making restructured dendrites and spines in adultborn neurons, consistent with activity-dependent neuronal recruitment. These findings identify a novel role for neurogenesis in decisions about future rewards, which is compromised in disorders where shortsighted gains are preferred at the expense of long-term health. MAIN TEXTAdult neurogenesis in the dentate gyrus (DG) subregion of the hippocampus has been implicated in psychiatric disorders such as depression 1 but it remains unclear exactly which behavioral processes depend on new neurons, due to the complex and heterogeneous nature of the disorder. For example, one of the core symptoms of depression is anhedonia, often defined as diminished pleasure or interest in pleasurable activities 2 . However, many behavioral processes are subsumed under this broad definition 3 . Relative to controls, depressed patients place less value on future rewards, which may shift behaviors away from optimal, but delayed, outcomes 4 . Altered prospective behaviors may result from hippocampal deficits. Indeed, hippocampal activity patterns reflect future-oriented behaviors in both rodents 5-7 and humans 8,9 , amnesics have an impoverished imagination of possible future events 10 and hippocampal damage biases humans 11,12 and animals [13][14][15] towards immediately-available rewards, at the expense of larger, but delayed, rewards. Whether adult neurogenesis contributes to choices about future rewards is unknown. However, blocking neurogenesis in mice reduces sucrose preference 16 , consistent with a possible role in the anhedonic symptoms of depression.To test the role of adult neurogenesis in future reward choice, we took advantage of the transgenic GFAP-TK rat model to deplete neurogenesis 17 , and operant tasks that have been optimized for rats. As measured by the immature neuronal marker, DCX, neurogenesis was reduced in valganciclovirtreated (VGCV) TK rats by 94% in the dorsal DG and 77% in the ventral DG, compared to wild type (WT) rats (Fig. 1A-F). Blockade of neurogenesis reduced the overall volume of the dentate granule cell layer, consistent with DG atrophy in depressed patients 18,19 , but was without noticeable effect on subventricular zone neurogenesis, likely due to faster recovery in this neurogenic region during the VGCV-free period of operant testing (Supplementary Fig. 1 and Supplementary Fig. 2).Delayed rewards typically have less subjective value than immediately-available rewards, a phenomenon often referred to as delay discounting (DD) 20 . To determine if adult neurogenesis regulates the value of delayed rewards, we used a rodent DD paradigm where rats choose between a small reward (1 sugar pellet) that is delivered im...

The dentate gyrus is essential for remembering the fine details of experiences that comprise episodic memory. Dentate gyrus granule cells receive highly-processed sensory information and are hypothesized to perform a pattern separation function, whereby similar sensory inputs are transformed into orthogonal neural representations. Behaviorally, this is believed to enable distinct memory for highly interfering stimuli. Since the dentate gyrus is comprised of a large number of adult-born neurons, which have unique synaptic wiring and neurophysiological firing patterns, it has been proposed that neurogenesis may contribute to this process in unique ways. Some behavioral evidence exists to support this role, whereby neurogenesis-deficient rodents are impaired at discriminating the fine visuospatial details of experiences. However, the extent to which newborn neurons contribute to dentate gyrus-dependent learning tasks is unclear. Furthermore, since most studies of dentate gyrus function are conducted in male rats, little is known about how females perform in similar situations, and whether there might be sex differences in the function of adult neurogenesis. To address these issues, we examined spatial discrimination memory in transgenic male and female rats that lacked adult neurogenesis. The first task probed memory for the position of local objects in an open field, assessed by behavioral responses to novel object locations. The second task examined memory for distal environmental cues. All rats were able to successfully discriminate local and distal cue changes. Males and females also performed comparably, although females displayed higher levels of rearing and locomotion. Collectively, our results indicate that rats are capable of learning about local and distal cues in the absence of adult neurogenesis.