Bernstein Seminars March-April 2022

April 12th from 17h15 to 18h

Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear.

 Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV⁺-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV⁺-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV⁺-IN synapses were important for maximum effectiveness.

 Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks

https://www.bcf.uni-freiburg.de/events/bernstein-seminar/2022/20220412_jonas

Apr. 5th from 17h15 to 18h

Antonio Fernandez Ruiz: Hippocampal cellular diversity supports flexible computational demands

Animals use memories of previous experiences to guide behavior in a flexible manner. During behavior, hippocampal principal cells are tuned to specific locations in the environment (‘place cells’). The same cells that encoded recent spatial experiences are reactivated during sleep and rest periods, coordinated by synchronous network events known as sharp-wave ripples (SWRs). The sequential activation of hippocampal place cells during behavior and their subsequent reactivation during ‘offline’ periods are considered one of the cellular hallmarks of memory.

Recent studies have highlighted that hippocampal principal cells, traditionally considered as a highly homogeneous cell type, are indeed very diverse in their morphology, physiology and connectivity. However, most studies on the hippocampal mechanisms of memory to date did not take into account this cellular diversity. We hypothesize that it is precisely the functional diversity of hippocampal principal cells that supports its remarkable mnemonic capacities.

In this talk, I am going to present recent evidence supporting this hypothesis. We recorded and manipulated hippocampal and cortical neuronal ensembles in rats performing navigation and learning tasks. We found that hippocampal cell types express different spatial codes and synchronize with distinct brain regions based on behavioral demands. The precise temporal coordination among distributed cell ensembles emerged as a fundamental mechanism for learning and memory. We propose that the functional diversity of hippocampal principal cells and their dynamic modulation support the remarkable learning flexibility that rodents and other animals display.

https://www.bcf.uni-freiburg.de/events/bernstein-seminar/2022/20220405_ruiz

March 22nd from 17h15 to 18h

Tracking heading direction within an environment is a fundamental requirement for flexible, goal-directed navigation. In insects, a conserved brain region called the central complex creates a head direction representation that acts like a neural compass and that can guide the animal’s movements. In fruit flies, we can monitor this compass circuitry using two-photon calcium imaging of genetically targeted neuron populations in head-fixed animals behaving in virtual reality (VR). Using this approach, it has been shown that the insect head direction representation is updated based on self-motion cues and external sensory information. Thus far, mechanisms for updating the fly’s neural compass using external sensory information has mainly been studied in relatively simple VR settings that give flies control over the angular position of static sensory environments.

 Under natural settings, however, sensory signals used by an animal to orient may temporarily disappear, for example when clouds hide the sun. Further, when moving through an environment, prominent landmarks can move independently from the from animal’s changes in head direction due to motion parallax, creating potentially conflicting stimuli. Based on connectomic analysis of the fly’s central complex circuitry, I identified potential circuit motifs for selecting and combining sensory cues to generate a head direction estimate in complex, multimodal environments. To test some of these predictions, I developed a VR system for flies based on the unity game engine.

 This VR system allowed me to monitor the fly’s compass circuitry using calcium imaging, while the animal navigates in cluttered, immersive environments with approachable local landmarks. I characterized the stability of the fly’s neural compass in different sensory environments and describe conditions under which flies can form a consistent HD estimate – a requirement for goal-directed navigation over extended periods of time. Going forward, I aim to link the dynamics of the HD representation to the processing and representation of sensory inputs.

https://www.bcf.uni-freiburg.de/events/bernstein-seminar/2022/20220322_haberkern

March 15th from 17h15 to 18h

GABA depolarize immature neurons close to the action potential (AP) threshold in development and adult neurogenesis. Nevertheless, GABAergic synapses effectively inhibit AP firing in newborn granule cells of the adult hippocampus. To investigate the underlying mechanisms, we have analyzed GABAergic inputs from soma-targeting parvalbumin and dendrite-targeting somatostatin interneurons.

Surprisingly, both interneuron subtypes activate α5-subunit containing GABAA receptors (α5-GABAARs) in young neurons, showing a nonlinear voltage-dependent activation with large conductance around the AP threshold. By contrast, in mature cells, parvalbumin interneuron synapses lack α5-subunits, while somatostatin interneurons continue to target nonlinear α5-GABAARs. Computational modelling shows that the voltage-dependent amplification of α5-GABAAR opening in young neurons is crucial for inhibition of AP firing to generate balanced and sparse firing activity, even with depolarized GABA reversal potential.

https://www.bcf.uni-freiburg.de/events/bernstein-seminar/2022/20220308_bischofberger

March 8th from 17h15 to 18h

Josef Bischofberger: GABAergic signaling in newborn granule cells of the adult hippocampus

GABA depolarize immature neurons close to the action potential (AP) threshold in development and adult neurogenesis. Nevertheless, GABAergic synapses effectively inhibit AP firing in newborn granule cells of the adult hippocampus. To investigate the underlying mechanisms, we have analyzed GABAergic inputs from soma-targeting parvalbumin and dendrite-targeting somatostatin interneurons.

 Surprisingly, both interneuron subtypes activate α5-subunit containing GABAA receptors (α5-GABAARs) in young neurons, showing a nonlinear voltage-dependent activation with large conductance around the AP threshold. By contrast, in mature cells, parvalbumin interneuron synapses lack α5-subunits, while somatostatin interneurons continue to target nonlinear α5-GABAARs. Computational modelling shows that the voltage-dependent amplification of α5-GABAAR opening in young neurons is crucial for inhibition of AP firing to generate balanced and sparse firing activity, even with depolarized GABA reversal potential.

https://www.bcf.uni-freiburg.de/events/bernstein-seminar/2022/20220308_bischofberger

Zoom Meeting. You can contact Fiona Siegfried for meeting ID and password.

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