Basal amygdala (BA) neurons guide associative learning via acquisition of responses to stimuli that predict salient appetitive or aversive outcomes. We examined the learning-and statedependent dynamics of BA neurons and ventral tegmental area dopamine axons that innervate BA (VTA DA➜BA ) using two-photon imaging and photometry in behaving mice. BA neurons did not respond to arbitrary visual stimuli, but acquired responses to stimuli that predicted either rewards or punishments. Most VTA DA➜BA axons were activated by both rewards and punishments, and acquired responses to cues predicting these outcomes during learning. Responses to cues predicting food rewards in VTA DA➜BA axons and BA neurons in hungry mice were strongly attenuated following satiation, while responses to cues predicting unavoidable punishments persisted or increased. Therefore, VTA DA➜BA axons may provide a reinforcement signal of motivational salience that invigorates adaptive behaviors by promoting learned responses to appetitive or aversive cues in distinct, intermingled sets of BA excitatory neurons.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:

38Basal amygdala (BA) neurons guide associative learning via acquisition of responses to stimuli 39 that predict salient appetitive or aversive outcomes. We examined the learning-and state-40 dependent dynamics of BA neurons and ventral tegmental area dopamine axons that innervate 41 BA (VTA DAàBA ) using two-photon imaging and photometry in behaving mice. BA neurons did not 42 respond to arbitrary visual stimuli, but acquired responses to stimuli that predicted either rewards 43 or punishments. Most VTA DAàBA axons were activated by both rewards and punishments, and 44 acquired responses to cues predicting these outcomes during learning. Responses to cues 45 predicting food rewards in VTA DAàBA axons and BA neurons in hungry mice were strongly 46 attenuated following satiation, while responses to cues predicting unavoidable punishments 47 persisted or increased. Therefore, VTA DAàBA axons may provide a reinforcement signal of 48 motivational salience that invigorates adaptive behaviors by promoting learned responses to 49 appetitive or aversive cues in distinct, intermingled sets of BA excitatory neurons. 128signal for promoting acquisition of responses to salient cues in BA neurons. As compared to LA, 129BA expresses higher levels of D1 receptors 23,24 ( Supplementary Fig. 3a,b) and receives denser 130 input from VTA dopamine axons ( Fig. 2a; Supplementary Fig. 3c). To monitor the activity of 131 VTA DAàBA axons, we selectively expressed GCaMP6s in VTA dopamine neurons (in DAT-IRES- 132Cre mice) and placed an optic fiber above the BA, allowing bulk photometry recording of activity 133 from VTA DAàBA axons ( Fig. 2b; Supplementary Fig. 4). 134Consistent with prediction error signals reported in VTA dopamine neurons 25,26 , VTA DAàBA 135 axon activity increased to reward delivery early in training ( Supplementary Fig. 5a). Once mice 136 achieved high task performance, VTA DAàBA axon responses shifted to tracking the RC 137 ( Supplementary Fig. 5b-e). RC responses were tightly locked to cue onset, and not to onset of 138 cue-induced licking (Fig. 2c). Following satiation, RC responses were strongly attenuated ( Fig. 139 2d-e). Sham satiation and home-cage caloric repletion experiments confirmed that this RC 140 response attenuation was not due to incidental factors such as fatigue or stress, which might differ 141 between early and late epochs of a given recording session ( Fig. 2f-h). In contrast, the NC and 142 AC-Av rarely elicited operant behavior in trained mice and did not evoke substantial responses in 143 any state ( Fig. 2d-e). 144These findings suggested that VTA DAàBA axons might signal salient outcomes and, 145 subsequently, cues that predict salient outcomes. Supporting this hypothesis, we observed that 146 during early training sessions with high false alarm rates, VTA DAàBA axons were also activated by 147 the quinine cue and quinine delivery ( Supplementary Fig. 5f-i). While dopamine is known to be 148 involved in amygdala plasticity during aversive associative conditioning 7,27 , direct evidence...

No abstract

Salient experiences are often relived in the mind. Human neuroimaging studies suggest that such experiences drive activity patterns in visual association cortex that are subsequently reactivated during quiet waking. Yet, the circuit-level consequences of such reactivations remain unclear. Here, we imaged hundreds of neurons in visual association cortex across days as mice learned a visual discrimination task. Distinct patterns of neurons were activated by different visual cues. These same patterns were subsequently reactivated during quiet waking in darkness, with higher reactivation rates during early learning and for food-predicting vs. neutral cues. Reactivations involving ensembles of neurons encoding both the food cue and the reward predicted strengthening of next-day functional connectivity of participating neurons, while the converse was observed for reactivations involving ensembles encoding only the food cue. We propose that task-relevant neurons strengthen, while task-irrelevant neurons weaken their dialogue with the network via participation in distinct flavors of reactivation.