Biology subjects

Bitterman, Y.

Publications and source records attributed to Bitterman, Y..

4 recordsLinked to original sources

bioRxiv2025

A common neuronal basis for Pavlovian and instrumental learning in amygdala circuits

Reward-predictive Pavlovian cues can selectively invigorate instrumental behaviors. Accumulating evidence pinpoints the basolateral amygdala (BLA) as a key brain structure to assign outcome-specific motivational significance to Pavlovian cues or Instrumental actions. However, whether neuronal representations of Pavlovian and Instrumental learnings are processed in different BLA circuits and how the resulting memories interact is unknown. Here, we used calcium imaging and optogenetic manipulation of the BLA neurons in mice that acquired and expressed Pavlovian and Instrumental behaviors in a multi-phase behavioral task called specific Pavlovian to Instrumental Transfer (sPIT). We first confirmed that Pavlovian cues selectively invigorate instrumental actions and showed that this effect, referred as the sPIT effect, depends on BLA activity. Then, by tracking the activity of single BLA neurons across days, we found that BLA neurons integrate common reward-anticipation information relevant for Pavlovian and instrumental learning. Interestingly, this reward-anticipation information re-emerged during subsequent memory transfer and covaried with sPIT effect. These findings reveal that the BLA encodes an outcome-specific motivational state that generalizes across Pavlovian and instrumental behaviors to promote and guide reward-seeking behavior.

neuroscience↗

bioRxiv2024

Heterogeneous plasticity of amygdala interneurons in associative learning and extinction

Neural circuits undergo experience-dependent plasticity to form long-lasting memories. Excitatory projection neurons are considered to be the primary neuronal substrate for memory acquisition and storage. However, inhibitory interneurons control the activity of projection neurons in a in a spatially and temporally precise manner, yet their contribution to memory acquisition, storage and expression remains poorly understood. Here, we employ a miniature microscope imaging approach to monitor the activity of large amygdala interneuron populations in freely moving mice during fear learning and extinction at the single cell level. We find that amygdala interneurons display mixed-selectivity and show complex plastic responses at both the ensemble and single neuron level across the acquisition, expression and extinction of aversive memories. In contrast to bidirectional single cell plasticity across distinct fear states, learning-induced changes at the population level occur transiently during conditioning and do not consolidate across days. Examining molecular interneuron subpopulations revealed that disinhibitory vasoactive intestinal peptide (VIP) expressing cells are predominantly activated by high fear states. In contrast, somatostatin (SST) interneurons display a preference for safety cues and thereby suppress excitatory neuron responsiveness. However, responses of individual neurons within the SST and VIP populations are non-uniform, indicating the presence of functional subtypes within classical molecularly-defined interneuron populations. Taken together, we identify complex neuronal plasticity within amygdala interneuron ensembles that goes beyond a passive processing function, suggesting a critical role of inhibitory microcircuit elements for memory selectivity and stability.

neuroscience↗

bioRxiv2018

Adaptive disinhibitory gating by VIP interneurons permits associative learning

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.

neuroscience↗

bioRxiv2018

Amygdala neuronal ensembles dynamically encode behavioral states

Internal states, including affective or homeostatic states, are important behavioral motivators. The amygdala is a key brain region involved in the regulation of motivated behaviors, yet how distinct internal states are represented in amygdala circuits is unknown. Here, by imaging somatic neural calcium dynamics in freely moving mice, we identify changes in the relative activity levels of two major, non-overlapping populations of principal neurons in the basal nucleus of the amygdala (BA) that predict switches between exploratory and non-exploratory (defensive, anxiety-like) behavioral states across different environments. Moreover, the amygdala widely broadcasts internal state information via several output pathways to larger brain networks, and sensory responses in BA occur independently of behavioral state encoding. Thus, the brain processes external stimuli and internal states in an orthogonal manner, which may facilitate rapid and flexible selection of appropriate, state-dependent behavioral responses.

neuroscience↗