Past events

Drosophila melanogaster flies show complex behaviors like associative learning. Combining the available genetic tools with behavioral measures allows us to study the specific neuronal circuits of learning and memory. Using olfactory conditioning, I directly compared the neuronal circuit of memories with different punishment paradigms: the widely used electric-shock and the newly established elevated temperature. I identified the neural pathway selectively required for olfactory-temperature conditioning, from the sensory input to the central neurons signaling reinforcement. I found that temperature and electric-shock punishments—despite being perceived by distinct sensors—eventually converge to the same neuronal network: the dopamine pathway. Thus the role of dopamine is general—attaching a motivational value to an environmental stimulus. This finding is especially significant in context of recent findings in mammalian systems, namely that in addition to their well-established role in signaling positive reinforcement, dopaminergic populations in the mammalian brain were also shown to represent aversive reinforcement.

Summary: Gyorgy Buzsaki aims at understanding how neuronal circuitries of the brain support its cognitive capacities, with a primary interest in brain oscillations, synchronization and memory. His major goal is to provide rational, mechanistic explanations of cognitive functions at a descriptive level. Over the past 35 years, Buzsaki has led the way in analyzing the functional properties of cortical neurons acting within their natural networks. He pioneered the experimental exploration of how coordinated, rhythmic neuronal activity serves physiological functions in the cerebral cortex, and in particular, how information is exchanged between the hippocampus and neocortex. For this aim, Buzsaki's lab has established some of the most difficult approaches necessary to solve these problems. His work includes innovative techniques to monitor neural activity and brain oscillation in behaving rodents from the cellular level to whole network activation. In addition to his numerous publications and reviews, Gyorgy Buzsaki is the author of the book "Rhythms of the Brain", which discusses mechanisms and functions of neuronal synchronization. He explains the field of brain oscillations, and how oscillatory timing is the brain’s fundamental organizer of neuronal information. Among many other distinguished awards, he is the recipient of the 2011 European brain prize. http://www.buzsakilab.com/

The etiology of schizophrenia is complex and largely unknown, but consistent findings report a strong genetic component. While several potential schizophrenia-susceptibility genes have been identified, effect sizes are very small and replication is inconsistent, likely because of the complexity of human polymorphisms, genetic and clinical heterogeneity and the potential uncontrollable impact of gene-gene and gene-environment interactions. In this context, mutant mice bearing targeted mutations of schizophrenia-susceptibility genes are unique tools to elucidate the neurobiological basis of this devastating disorder. Using COMT*dysbindin-1 double mutant mice, we investigated the COMT*dysbindin-1 gene-gene interacting effects in the expression of rodents’ correlates of schizophrenia-relevant behavioral abnormalities. A major focus of our work is centered on how to dissect higher order cognitive functions in mice with high translational validity to human studies. In particular, in contrast to single genetic modifications, the combined decreased activity of both COMT and dysbindin-1 produced marked working memory, recency memory and attentional set-shifting deficits, and amphetamine supersensitivity; all abnormalities ascribed as mice’ correlates of schizophrenia-like symptoms. Based on this, we found evidence of the same non-linear genetic interaction in prefrontal cortical function in humans. Finally, to disentangle how COMT*dysbindin-1 interaction might converge in dopaminergic signaling, we measured in these double mutant mice dopamine levels in the PFC and dorsal striatum by in vivo microdialysis. Interestingly, concomitant COMT*dysbindin-1 reduction diminished dopamine levels in PFC and striatum, while amphetamine-evoked dopamine increase was attenuated in the PFC but exacerbated in the striatum. These findings illustrate a clinically relevant experimental animal model based on a predicted epistatic interaction of two schizophrenia-susceptibility genes and unravel interesting genetic mechanisms in the etiology of this mental illness.

I will discuss techniques that allow us to perform cellular and subcellular resolution imaging of neuronal activity in mice navigating in virtual reality environments and recent results from imaging place cells and grid cells. I will describe activity patterns that we have observed in hippocampal place cell dendrites and the implications for how associative Hebbian learning may take place during behavior. I will also describe the functional micro-organization of grid cells in the medial entorhinal cortex and what the organization might tell us about the circuits that generate grid cell firing patterns.