Biology subjects

Krabbe, S.

Publications and source records attributed to Krabbe, S..

5 recordsLinked to original sources

bioRxiv2026

Basolateral amygdala dopamine signals behavioural salience across exploration and learning

Animals must balance exploration with threat avoidance, yet how neuromodulatory signals shape information-seeking states remains unclear. Using fibre photometry recordings in the basolateral amygdala in freely moving mice, we show that dopamine release is selectively elevated during self-initiated exploratory actions, adapts with repeated exposure, and tracks the behavioural relevance of predictive cues in associative learning and extinction. Our results advance current models of amygdala dopamine function by suggesting that it conveys a state-dependent salience signal that highlights behaviourally relevant moments arising from both environmental cues and self-generated exploration, thereby priming amygdala circuits for plasticity.

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↗

bioRxiv2022

Multimodal mapping of cell types and projections in the central nucleus of the amygdala

The central nucleus of the amygdala (CEA) is a brain region that integrates external and internal sensory information and executes innate and adaptive behaviors through distinct output pathways. Despite its complex functions, the diversity of molecularly defined neuronal types in the CEA and their contributions to major axonal projection targets have not been examined systematically. Here, we performed single-cell RNA-sequencing (scRNA-Seq) to classify molecularly defined cell types in the CEA and identified marker-genes to map the location of these neuronal types using expansion assisted iterative fluorescence in situ hybridization (EASI-FISH). We developed new methods to integrate EASI-FISH with 5-plex retrograde axonal labeling to determine the spatial, morphological, and connectivity properties of [~]30,000 molecularly defined CEA neurons. Our study revealed spatio-molecular organization of the CEA, with medial and lateral CEA associated with distinct cell families. We also found a long-range axon projection network from the CEA, where target regions receive inputs from multiple molecularly defined cell types. Axon collateralization was found primarily among projections to hindbrain targets, which are distinct from forebrain projections. This resource reports marker-gene combinations for molecularly defined cell types and axon-projection types, which will be useful for selective interrogation of these neuronal populations to study their contributions to the diverse functions of the CEA.

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↗