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Marian Tsanov research specific

Tsanov lab

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Marian Tsanov

Marian Tsanov

 

Specific research interests

 

1. Septo-hippocampal information processing of spatial navigation and reward.
The medial septal is described here as a circuitry that mediates not only sustained attention and path integration but also reinforcement learning. Recent data from my lab show that optogenetic photoexcitation of septal neurons triggeres navigation preference and hippocampal place field ramepping. This is on-going reseach project with preliminary data: the movie below shows navigation in rectangular-shaped linear track of rat with chronically-implanted tetrodes in hippocampus. The first half of the video shows pre-ChR2 session, measuring baseline behavioral and electrophysiological activity signals. The second half of the video shows light delivery, triggering photoexcitation of septal neurons. The coordinates of photostimulation (ChR2 arms) are denoted in blue:

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2. Monoaminergic and cholinergic modulation of hippocampal plasticity and oscillations.
Hippocampal spatial properties crucially depend on the neuromodulatory inputs. Here, we investigate the effects of cholinergic and dopaminergic inputs on spatial memory and synaptic plasticity in rats. In order to evaluate the influence of modafinil on rats’ spatial performance, we have explored in this study the spatial properties of hippcampal neurons in transgenic rats.The hippocampal region is believed to play a key role in the formation of episodic memories (in particular spatial memory), and long-term synaptic plasticity is generally accepted as the mechanism underlying experience-dependent alterations in hippocampus. Thus, the second objective of the lab is to examine the effect of ChAT-neurons on hippocampal synaptic plasticity and oscillations, using optogenetic stimulation of cholinergic cells in medial septum.

Place cells Marian Tsanov

Place cells recorded in hippocampus of behaving rat in rectangular-shaped linear track (modified from Tsanov et al., 2014)

3. Inter-regional synaptic integration of sensorimotor signals within the episodic memory networks.
Our current understanding of episodic memory formation proposes that external events (including sensory and motor signals) are unified into temporal episodes within and beyond hippocampo-diencephalic circuitry. Hippocampal synaptic plasticity has been extensively explored, but there is little research on interregional neuronal communication, and how it reflects long-lasting changes in firing neuronal properties between regions. To investigate inter-regional synaptic integration, I will explore the effects of physiological and stimulation-triggered plasticity on postsynaptic firing frequencies (with a particular focus on theta rhythmicity). Here, we will focus especially on the under-explored habenular and entopeduncular nuclei (using path integration-based paradigms), as these nuclei provide the anatomical locus for cross-talk between striatal and hippocampal memory systems. Theta rhythm serves a critical role in the mnemonic functions of the hippocampal system, with the theta cycle implicated as an information quantum.

thalamic theta cell

Cholinergic theta cell recorded in medial septum during different behavioral states (modified from Tsanov et al., 2014)

4. Computational investigation of neuronal biophysical properties in the septo-hippocampal networks.
The other project that comprises my current interests, applies computation approach to simulate the link between byophysical neuronal properties, firing patterns and synaptic plasticity. Synchronous oscillatory activity functionally links remote neuronal populations or brain areas, providing a temporal window for transient communication. Coupling oscillations between areas produces coincident firing precision necessary to enhance synaptic efficiency The anatomical focus of current proposal is septo-hippocampal axis. The benefit in modelling this circuitry is the extensive knowledge about anatomical connectivity as well as the electrophysiological properties of septal and hippocampal neuronal types. Additionally, my experience in septo-hippocampal single-unit activity and field oscillations would provide sufficient expertise to ascertain the model. My goal will be to link different synchronization model types and at the same time to understand the difference between the mechanisms that mediate local septal, local hippocampal and large-scale septo-hippocampal rhythm. I am using NEURON simulation software to relate the conuctance properties of membrane channels to the spiking profile of the cells in septo-hippocampal circuitry.

Neuron simulation

NEURON simulation environment

The one-compartmental Hodgking-Huxley model includes only the fundamental of ion channels that are considered essential to account for the experimental data. The basic currents include spike-generating currents (INa and IK) and slowly inactivating potassium current (IKS). The synaptic current Isyn represents synaptic interactions in network simulations. Using Hodgkin–Huxley type model we have recently showed here the importance of bursts in the turn-specific modulation of the directional tuning curve.

Phasic current simulation

Phsaic current injection to Hodgkin-Huxley cell model (Tsanov et al., 2014)

We also aim is to investigate the frequency control and synchronization of the modelled neurons when coupled by excitatory, inhibitory and neuromodulatory synapses and controlled by convergent synaptic inputs. We will investigate how the fraction of the network population that is composed of intrinsic bursters affects measures of rhythmogenic capacity or “robustness” of network activity. The input range is the size of parameter space where networkwide synchronous rhythmic bursting occurs and the output range is the range of bursting frequencies that the network produces across this input range. Network simulations of pairs of identical cells will evaluate if increasing tonic excitation augments the frequency of synchronous bursting.

5. Investigation of hippocampo-diencephalic interaction in the formation of episodic memory.
Ongoing project in our lab is an interdisciplinary research that explores the anatomical and physiological connections between different hierarchical levels of the sequences encoding. One of the projects in our lab explores the experience-dependent changes of synaptic and non-synaptic properties of information processing along the hippocampo-thalamic and hippocampo-hypothalamic connections. The main goal of this research is to reveal the functional significance of archicortical-diencephalic loop in memory formation. I am investigating the properties of head-direction cells during distinct behavioral episodes, which allow us to gain an insight of what information is encoded in the directional signal. One of the behavioral investigation of head-direction system includes investigation of the thalamic activity during high-voltage spindles.

Spindles

The firing patterns of thalamic head-direction cell (upper panel) are shown during high-voltage spindle epochs identified by the power spectrogram (middle panel) and oscillation (lower panel) profile (Tsanov et al., 2014)

 


General Research Interests

Marian Tsanov publications

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