Systems mechanisms of learning and memory
Our research is focused on the mechanisms of information representation and propagation within and across different cortical networks. Specifically, we are exploring the neurophysiological mechanisms of information transfer within and between the neocortex and hippocampus during learning (acquisition) and sleep (consolidation), as one of the key topics in learning and memory research.
We employ state-of-the-art multichannel extracellular recordings in different cortical areas in behaving rats. Recordings with multichannel silicon probes allow us to sample the activity of multiple single neurons and local field potentials across multiple layers of one or several cortical areas. We also employ various perturbation techniques, such as electrical stimulation and optogenetic modulation of neuronal activity. We aim employ behavioral paradigms and animal tracking methods that allow for quantitative and precise control of animal behavior. Our research involves advanced signal processing and data mining, as well as computational modeling.
Projects in the lab are covering several overlapping topics:
Network dynamics and population coding in entorhino-hippocampal circuits
By combining recordings with different types of multichannel electrodes simultaneously from the same anatomical region we investigate the link between local dynamics (gamma oscillations) within entorhino-hippocampal networks and the representation of the environment by sequential activation of cell ensembles in these networks during spatial navigation, memory tasks and sleep.
This project will lead to a better understanding of the relationship between place cells activity, phase precession, hippocampal sequences and the ongoing oscillatory activity (theta and gamma oscillations). This topic is the central problem in current state of hippocampal research on spatial navigation and memory. In addition, we investigate the integration of multiple streams of information (“what” and “where”) in the hippocampal networks coming from lateral and medial entorhinal cortices. We are extending behavioral paradigms to study integration of sensory inputs into hippocampal representation using precise control of the olfactory (supported by the DFG Priority Program Grant) and somatosensory (collaboration with Ehud Ahissar, Weizmann University) inputs.nach oben
Quantitative analysis of spontaneous exploratory behavior and hippocampal dynamics
Behavioral strategies and patterns that rodents use to sample their environment during learning are very diverse and complex. Yet, investigations of functional neural mechanisms of spatial navigation and memory generally ignore this diversity and suffer from crude temporal and spacial resolution. We developed experimental tools for joint analysis of behavior in freely moving rat and hippocampal network dynamics on a fine temporal (100 - 400 msec) and spatial scale, that allow us to classify the rats behavior beyond the commonly used 2-d position.
We perform recordings of multiple single neurons and local field potentials in hippocampus in conjunction with high resolution tracking and quantitative segmentation and classification of exploratory behavioral patterns (rearing, crouching, head turning, sniffing, etc) in freely moving rats. This approach allows us to identify neural dynamics that is associated with stereotypic and often subtle behavioral states in a quantitative and temporally precise ways. Extension of the methodology to transgenic mice in combination with new generation silicon-based multiplexing arrays is supported by a DFG Priority Program.nach oben
Methodological advancements of network dynamics characterization
We aim to identify neural dynamics associated with sensory processing of relevant stimuli in freely moving rats exploring the environment or performing a task. To this end we developed novel high-density extracellular electrodes that for the first time allow us to sample the activity of populations of neocortical neurons across all layers in one single column. In addition, we sample topographic cortical dynamics across larger cortical areas using flexible subdural arrays. Further, to probe and perturb neocortical dynamics we combine these recordings with optogenetic stimulation using miniature movable optrodes efficiently driven by light-emitting diodes.
In our effort to identify local network dynamics during a behavioral task on a single trial basis we are developing novel tools that allow us to combine conventional electrophysiological approaches (multichannel extracellular arrays) and optical redout of specific population dynamics. For this we developed minimally invasive optical probes that allows readout of fluorescent signal from genetically encoded voltage and calcium indicators from deep brain areas in freely moving rodents. This development will greatly improve specificity and the degree of localization of the readout of neural signals.nach oben
Mechanisms of memory consolidation during sleep
We are continuing to work on the analisis of neuronal dynamics across neocortex, entorhinal cortex and hippocampus during sleep and its function in memory consolidation.
Development of somatosensory system
Internally generated oscillatory dynamics is important during development. What is the functional importance of the kicking of human fetus? In collaboration with R. Khazipov and X. Leinekugel in G. Buzsaki lab we established that early neonatal twitches (spontaneous involuntary movements) in rat pups are followed by topographically specific oscillatory spindle-bursts in the somatosensory cortex (Khazipov et al, 2004). This phenomenon is a result of twitching-triggered sensory feedback from the periphery to the cortex, which allows the brain to coordinate the development of mapping the motor layout onto the sensory representation of the body. Since this study, the existence of the coordination of early peripheral and cortical activity have been documented in other modalities in rodents and in human preterm babies, suggesting that this is a universal developmental mechanism.
Recent work that came out of the collaboration of R. Khazipov's and my laboratory demonstrated that more finely localized sensory input (single whisker movement) gives rise to topographic gamma (40-60 Hz) oscillatory bursts, which are instrumental in the development of topographic columnar thalamo-cortical connections (Minlebaev et al, 2011).