Learning drives behavioral adaptations necessary for survival. While plasticity of excitatory projection neurons during associative learning is studied extensively, little is known about the contributions of local interneurons. Using fear conditioning as a model for associative learning, we find that behaviorally relevant, salient stimuli cause learning by tapping into a local microcircuit consisting of precisely connected subtypes of inhibitory interneurons. By employing calcium imaging and optogenetics, we demonstrate that vasoactive intestinal peptide (VIP)-expressing interneurons in the basolateral amygdala are activated by aversive events and provide an instructive disinhibitory signal for associative learning. Notably, VIP interneuron responses are plastic and shift from the instructive to the predictive cue upon memory formation. We describe a novel form of adaptive disinhibitory gating by VIP interneurons that allows to discriminate unexpected, important from irrelevant information, and might be a general dynamic circuit motif to trigger stimulus-specific learning, thereby ensuring appropriate behavioral adaptations to salient events..

Internal states, including affective or homeostatic states, are important behavioral motivators. The amygdala regulates motivated behaviors, yet how distinct states are represented in amygdala circuits is unknown. By longitudinally imaging neural calcium dynamics in freely moving mice across different environments, we identified opponent changes in activity levels of two major, nonoverlapping populations of basal amygdala principal neurons. This population signature does not report global anxiety but predicts switches between exploratory and nonexploratory, defensive states. Moreover, the amygdala separately processes external stimuli and internal states and broadcasts state information via several output pathways to larger brain networks. Our findings extend the concept of thalamocortical “brain-state” coding to include affective and exploratory states and provide an entry point into the state dependency of brain function and behavior in defined circuits.

Just-noticeable differences of physical parameters are often limited by the resolution of the peripheral sensory apparatus. Thus, two-point discrimination in vision is limited by the size of individual photoreceptors. Frequency selectivity is a basic property of neurons in the mammalian auditory pathway 1,2 . However, just-noticeable differences of frequency are substantially smaller than the bandwidth of the peripheral sensors 3 . Here we report that frequency tuning in single neurons recorded from human auditory cortex in response to random-chord stimuli is far narrower than that typically described in any other mammalian species (besides bats), and substantially exceeds that attributed to the human auditory periphery. Interestingly, simple spectral filter models failed to predict the neuronal responses to natural stimuli, including speech and music. Thus, natural sounds engage additional processing mechanisms beyond the exquisite frequency tuning probed by the randomchord stimuli.Sounds are decomposed to different frequency bands by the auditory periphery. Tonotopic ('by frequency') organization is kept throughout the auditory pathway, at least up to and including primary auditory cortex. In vision and somatosensation, the resolution of the peripheral sensors to a large degree determines overall behavioural discrimination capabilities. However, in the auditory system, frequency just-noticeable differences in well-trained subjects may be 30 times smaller than the presumed bandwidth of the peripheral filters ('critical bands', typically about a sixth of an octave in humans, as measured in psychoacoustical tests). Electrophysiological correlates of critical bands have been suggested 4-6 , and frequency just-noticeable differences can be derived by integrating information over a large population of neurons 7 , but there are currently no reports of a significant population of single neurons the bandwidth of which corresponds to the behavioural just-noticeable differences. Does the high-frequency resolution

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