Neuronal bases of cognitive and memory functions and dysfunctions

Investigating neural circuits that control reward learning is crucial if we want to understand healthy behavior or disorders like addiction.

…about the roles of small axons, whose size matches that of the majority cortical axons

…about the cellular interface between DG and CA3 regions

Fast, two- photon imaging with three-dimensional scanning of spine, dendritic and neuronal assemblies in behaving animals

Fast two-photon in vivo imaging with three-dimensional random-access scanning in large tissue volumes

High efficiency two-photon uncaging coupled by the correction of spontaneous hydrolysis

Determine the molecular specializations underlying the functional diversity of synapses, such as the probability and short-term plasticity of neurotransmitter release. In vitro electrophysiology, two-photon imaging, LM and EM immunolocalization are combined to address these issues.

Determining the location and density of various voltage- and ligand-gated ion channels in defined subcellular compartments of hippocampal pyramidal cells, using quantitative LM and EM immunolocalization. Perform multi-compartmental modeling to generate functionally testable predictions of the functional consequences of specialized ion channel distributions. In vitro electrophysiology and imaging approaches are used to test the functional predictions of our models.

In vivo two-photon [Ca2+] imaging are performed in head-restrained mice while performing navigation in virtual reality to functionally characterize distinct pyramidal cells. This is followed by post hoc in vitro electrophysiological and anatomical experiments to reveal differences in intrinsic properties and synaptic innervation of the functionally characterized nerve cells.

Prefrontal cortex plays a role in many higher order cognitive processes. 

In this project we investigate the local connections within the basolateral amygdala.

In vivo examination of age-dependent changes in the activity of basal forebrain cholinergic neurons during a Pavlovian conditioning task

The medial septum modulates hippocampal oscillations beyond the theta rhythm

In 2009 we described a novel form of modulation in the median raphe – hippocampus connection capable of selectively and rapidly recruiting a subset of inhibitory neurons. The function of this highly efficient form of modulation in shaping hippocampal representations is still unknown. In this project, we aim to unravel how the emergence and reorganization of hippocampal coding patterns linked to salient event is influenced by raphe-hippocampal rapid modulation.

Coding by transiently emerging co-active ensembles of neurons has long been a central tenet of neuroscience formulated in the influential assembly hypothesis. Accordingly, the animal’s actions can be predicted much more efficiently from the coordinated activity pattern of neurons than from the stimulus or event-locked spiking of single units. In contrast to cortical and hippocampal networks, assembly coding in subcortical modulatory circuits is almost fully unexplored. In this project, we aim to reveal and characterize the assembly code in the median raphe (MR), the source of ascending serotonergic neuromodulation of the limbic system. We expect to identify a fundamentally novel mode of neuromodulation whereby adaptive behavioral responses are controlled by the correlated activity of modulatory neuronal assemblies.

Subcortical modulation is an indispensable component of cortical function, and ultimately, is key for adaptive behavioral responses. Therefore, disruption of subcortical modulation leads to debilitating psychiatric conditions. A key but largely ignored area of research concerns the control of subcortical modulation by cortical feedback. In this project we explore how the top-down control of the median raphe by the prefrontal cortex controls memory-guided behaviors. Our hope is to identify a missing link in the process that leads from normal subcortical function to pathological cortical operation.

https://www.youtube.com/watch?v=3Lx2uHnOmHU

With our research activity we aim to contribute to the understanding of how distinct endocannabinoid-related signaling pathways regulate certain forms of synaptic plasticity.

One of the major endocannabinoid molecules is anandamide. In this research project we aim to characterize its non-canonical synthesis enzymes, Abhd4 and Gde1, and to describe their diverse physiological functions in the brain.

Our latest paper in Nature Communications presents the PharmacoSTORM method developed in our laboratory.

...about our contributions to the projects of other research groups

In vitro measurement of spontaneous neuronal network activity

Fast 3D imaging in behaving mice

Cortex- wide activation of VIP- expressing inhibitory neurons by reward and punishment

Restoration of visual perception by 3D artifical photostimulation

In this project we study the role of thalamus in motor learning.

In this project, we study the synaptic organization of the human thalamus.

In this project we study the diversity of interactions between cortex and thalamus.

Throughout life animals inevitably encounter unforeseen threatening events. Activity of principal cells in the hippocampus is tuned for locations and for salient stimuli in the animals’ environment thus, forming a map known to be pivotal for guiding behavior. Here, we investigate if a code corresponding to threatening stimuli exists in the CA1 region of the dorsal hippocampus.