Übersicht: MPI-BI Vorträge

Fast synaptic inhibition is one of the main driving forces determining neural output during behavior, yet its exact roles in controlling the activity of individual neurons is challenging to experimentally determine in vivo. The zebra finch is a powerful model system, linking precise premotor neuron output to a learned vocal motor skill – a stereotyped courtship song. Using intracellular and patch recordings, we explored the impact of inhibition on the premotor song network HVC. Local network inhibition gates premotor neuron output in adult song production and has the capacity to control plasticity in a learning dependent manner in juvenile birds. While single-cell electrophysiology is a valuable tool for correlating sub- and suprathreshold neural activity to behavior, it is still difficult to manipulate key genes such as ion channels causally relate intracellular mechanisms to neural function in vivo. To manipulate inhibition at the single-cell level within an otherwise intact network, we developed a method for targeted genetic modification of individual neurons in vivo. We used RNA single-cell electroporation for reliable gene delivery and CRISPR mediated knockout of the GABA-A receptor in neurons of mouse cortex. Individual neurons lacking GABA-A mediated inhibition experienced two distinct phases of adaptation. These studies demonstrate the value of single neuron recordings and manipulations in vivo to reveal unique insights into neural function in awake animals. [mehr]

Animals must robustly execute behaviors while remaining flexible enough to adapt when circumstances change. Over longer timescales, the circuits underlying behavior must evolve to match the animal's needs. Crucially, what makes a nervous system capable of this at both scales remains an open question. We study foraging behavior in nematodes to investigate these questions. Specifically, we use a grazing bacteriovore, the model nematode C. elegans, alongside an omnivorous species, P. pacificus that can prey on other nematodes. Despite their large large evolutionary divergence of over 100 My, the coarse structure of the nervous system remains sufficiently similar, allowing us to compare which structural and which neuromodulatory changes contribute to the behavioral divergence. We could recently show that changes in noradrenergic signaling underlie the evolution of predatory aggression, demonstrating that flexibility in the extrasynaptic modulatory signaling can be a powerful way to adapt and evolve novel behaviors. Theoretical modeling further supports this insight by showing that a biophysically inspired model of neuromodulation generates more robust and diverse states than models without neuromodulation. Building on this, we now investigate how coordinated changes in both synaptic and neuromodulatory signaling together shape the evolvability of behavior using behavioral assays, whole-brain functional imaging and computational models. [mehr]

Sensory receptors are at the interface between an organism and its environment and thus represent key sites for biological innovation. Octopuses are a rich source for biological novelty: they exhibit complex cognition and behavior similar to vertebrates but via entirely distinct organization and evolutionary history. Indeed, among the most unique octopus traits is a complex distributed nervous system that enables autonomous, chemosensory arm behavior. Our lab recently discovered a novel family of chemotactile receptors (CRs) that mediate “taste by touch” arm exploration. CRs diverged from neurotransmitter receptors to form pentameric ionotropic receptors that detect poorly soluble molecules for contact-dependent chemosensation. Here, I will describe our curiosity-based exploration of octopus “taste by touch” as a striking example of evolution that can be leveraged to understand the molecular basis of novelty across levels of biological organization. [mehr]

How do organisms control which proteins they make to drive distinct cellular functions? Every aspect of biology is defined by which proteins each cell expresses. Furthermore, to manifest diverse phenotypes, cells must regulate protein synthesis at both global and gene-specific levels. To address this fundamental question, we leverage diverse cells, viruses, and animals to identify unanticipated principles of mRNA translational control that confer species-specific evolutionary novelty. [mehr]

The intrinsic organization underlying the central cognitive role of the prefrontal cortex (PFC)is poorly understood. We approach organization by profiling the activity and spatial location of > 23,000 neurons recorded in awake mice. High-resolution activity maps of the PFC do not align with cytoarchitecturally defined subregions. Instead, spontaneous activity and tuning to choice during a behavioral task were both related to intra-PFC hierarchy, suggesting that connectivity, rather than cytoarchitecture, shapes the PFC’s activity landscape. Low-rate, regular spontaneous firing was a hallmark of the PFC and of high hierarchy. Surprisingly, choice tuning is over-represented in units displaying high spontaneous firing rates, linking connectivity-based hierarchy to distinct functional properties, in separate neuronal populations. Our data-driven approach provides a scalable roadmap to obtain an integrated view of activity, structure, and function in the brain, opening new avenues to explore functional organizations using single neuron activities across species and brain regions. [mehr]