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Gründemann, J.

Publications and source records attributed to Gründemann, J..

7 recordsLinked to original sources

A thalamic inhibitory circuit aligns sensory coding with learned value

Adaptive behavior requires sensory systems to prioritize cues that predict meaningful outcomes while suppressing irrelevant stimuli, but how relevance-based filtering is implemented along early sensory pathways remains unclear. Using deep brain two-photon imaging and causal circuit manipulations in mice performing an audiovisual detection task, we show that inhibition from thalamic reticular nucleus dynamically tunes sensory thalamus according to learned value. As animals learned stimulus-outcome associations, neurons in medial geniculate body developed biased responses favoring reward-predicting cues and suppressing non-rewarded stimuli. Silencing inhibitory input from thalamic reticular nucleus broadly disinhibited thalamic responses and abolished this value bias. Notably, stimulus identity decoding was unaffected by loss of inhibition. However, the geometry of MGB population activity was reorganized: coding axes rotated, action-related coding was strongly impaired, and thalamic representations became misaligned with learned behavioral readout. This altered population code impaired behavioral performance despite preserved sensory separability. Thus, inhibition of sensory thalamus by the reticular nucleus does not simply gate sensory throughput; it acts as a subcortical coding mechanism that aligns neuronal representations with learned value and behavioral goals, with implications for disorders of perception and cognition.

neuroscience↗

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↗

Network state changes in sensory thalamus represent learned outcomes.

Thalamic brain areas play an important role in adaptive behaviors. Nevertheless, the population dynamics of thalamic relays during learning across sensory modalities remain mostly unknown. Using a cross-modal sensory reversal learning paradigm combined with deep brain two-photon calcium imaging of large populations of auditory thalamus (MGB) neurons, we identified that MGB neurons are biased towards reward predictors independent of modality. Additionally, functional classes of MGB neurons aligned with distinct task periods and behavioral outcomes, both dependent and independent of sensory modality. During non-sensory delay periods, MGB ensembles developed coherent neuronal representation as well as distinct co-activity network states reflecting predicted task outcome. These results demonstrate flexible cross-modal ensemble coding in auditory thalamus during adaptive learning and highlight its importance in brain-wide cross-modal computations during complex behavior. SummaryDeep brain imaging reveals flexible network states of sensory thalamus predicting task outcome in mice.

neuroscience↗

Live imaging of excitable axonal microdomains in ankyrin-G-GFP mice

The axon initial segment (AIS) constitutes not only the site of action potential initiation, but also a hub for activity-dependent modulation of output generation. Recent studies shedding light on AIS function used predominantly post-hoc approaches since no robust murine in vivo live reporters exist. Here, we introduce a reporter line in which the AIS is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the native Ank3 gene. Using confocal, superresolution, and two-photon microscopy as well as whole-cell patch-clamp recordings in vitro, ex vivo, and in vivo, we confirm that the subcellular scaffold of the AIS and electrophysiological parameters of labeled cells remain unchanged. We further uncover rapid AIS remodeling following increased network activity in this model system, as well as highly reproducible in vivo labeling of AIS over weeks. This novel reporter line allows longitudinal studies of AIS modulation and plasticity in vivo in real-time and thus provides a unique approach to study subcellular plasticity in a broad range of applications.

neuroscience↗

Single cell plasticity and population coding stability in auditory thalamus upon associative learning

Cortical and limbic brain areas are regarded as centres for learning. However, how thalamic sensory relays participate in plasticity upon associative learning, yet support stable long-term sensory coding remains unknown. Using a miniature microscope imaging approach, we monitor the activity of populations of auditory thalamus (MGB) neurons in freely moving mice upon fear conditioning. We find that single cells exhibit mixed selectivity and heterogeneous plasticity patterns to auditory and aversive stimuli upon learning, which is conserved in amygdala-projecting MGB neurons. In contrast to individual cells, population level encoding of auditory stimuli remained stable across days. Our data identifies MGB as a site for complex neuronal plasticity in fear learning upstream of the amygdala that is in an ideal position to drive plasticity in cortical and limbic brain areas. These findings suggest that MGBs role goes beyond a sole relay function by balancing experience-dependent, diverse single cell plasticity with consistent ensemble level representations of the sensory environment to support stable auditory perception with minimal affective bias.

neuroscience↗

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↗

Central Amygdala Circuits Modulate Food Consumption Through A Positive Valence Mechanism

The complex behaviors underlying the pursuit and consumption of rewards are integral to an organisms survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is not well understood. The central nucleus of the amygdala (CeA) is implicated in feeding and reward behavior, but the specific neural players and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we define the neuronal mechanisms by which the CeA promotes consumption of food. We show, using in vivo activity manipulations and Ca2+ imaging, that CeA GABAergic neurons expressing the serotonin receptor 2a (Htr2a) modulate food consumption in multiple contexts, promote positive reinforcement and are active in vivo during eating. We demonstrate using electrophysiology, anatomical tracing methods and in vivo optogenetics that both intra-CeA and long-range circuit mechanisms underlie these functional effects. Finally, we show that CeAHtr2a neurons are poised to regulate food consumption through inputs from feeding-relevant brain regions. Our study highlights a mechanism by which defined CeA neural circuits positively regulate food consumption.

neuroscience↗