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Marian Tsanov research

Tsanov lab

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Marian Tsanov

Marian Tsanov

 

Research interests

 

My current work explores the expression of engram cells in context-dependent learning. The movie below represents expression of c-fos-dependent engram cells in hippocampal CA1 of non-transgenic rats after contextual learning. This work is on-going experimental programme in collaboration with Prof Tomas Ryan.

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One of the main approaches in my researchis to analyse how the information processing within the investigated circuitry is encoded within theta cycle and how this integration supports hippocampal memory function. My methodology further develops the investigation of theta oscillations and hippocampal spatial representation, using the advantage of optogenetic and multi-site ensemble recording techniques:

Optogenetic rat Marian Tsanov

My reseach targets different brain regions that are involved in the processing of context-dependent learning and episodic-like memory formation. I combine electrophysilogy with high precision of neuronal units identification over several days, optogenetics for specific regions (such as the basolateral complex of amygdala below), behavior for spatial and non-spatial tasks aquisition and immediate early genes expression for memory engrams in the limbic system.

Amygdala optogenetics

hSyn-ChR2-YFP expression in the basolateral amygdala of non-transgenic rats (Mamad et al., 2018)

My lab uses optogenetic tools in parallel with electrophysiological recordings in the context of rodent spatial behaviour. Optogenetic tools allow us to investigate the roles of differing neuronal subtypes in behavioural contexts:

ChR2-YFP expression in the medial septum of ChAT::Cre rats

ChR2-YFP expression in the medial septum of ChAT::Cre rats (Mamad et al., 2015)

Optical stimulation of genetically targeted neurons expressing light sensitive channelrhodopsin can be used as a rapid activator of neuronal firing with potential cell type selectivity. I Have applied septal stimulation of choline acetyltransferase Chat::Cre rat line with optogenetic laser stimulation after the injection of ChR2-YFP adeno-associated virus in the septal cholinergic neurons:

Raster plot from 40 repetitions of optically evoked time-locked responses of ChAT cell

Raster plot from 40 repetitions of optically evoked time-locked responses of ChAT cell (Mamad et al., 2015)

Neurons of a specific type can be identified among the numerous recorded neurons from their response to light, and subsequently, their firing pattern can be analysed in relation to the firing of other neurons, local field potential patterns and the animal's behaviour. I Have applied optogenetically-induced excitation and inhibition of tyrosine-hydroxylase positive neurons of ventral tegmental area (VTA) in TH::Cre rat line to control place preference behaviour:

VTA optogenetics Tsanov lab

High-magnification confocal 3D image of AAV8-EF1a-DIO-iC++-TS-EYFP expression in TH+ neuron in ventral tegmental area. YFP expression is green, TH-staining is red and nuclear staining DAPI is blue (Mamad et al., 2017). This work was conducted in collaboration with Karl Deisseroth (Stanford University).

I found evidence that the accumulation of the place fields mediates the learning of the reward context of the environment. Recent data from my lab reveal that the causal link between place field distribution and behavioral place preference is mediated by the tegmental dopaminergic activity. These findings shed a new light on the ability of hippocampal neurons to store the experience-dependent context reward value, enabling episodic memory for past experience to support future adaptive behavior:

Place field map Tsanov lab

3D color-coded firing rate map of a hippocampal place cell (Mamad et al., 2017). 3D place field images allow for better detection of experience-dependent and optogenetically-induced place field plasticity.

I have 3 major areas of research interest, as follows:

1. Systems Neuroscience - the investigation of cortico-hippocampal interaction in the formation of episodic memory.
Memory is not a specialized property of a limited set of cortical areas; rather, all areas of the cortex are capable of experience-dependent change over a wide range of time scales. Information storage and memory formation in the brain are processes that occur in each region starting with the early sensory areas and these processes are represented by a use-dependent long lasting increase or decrease in synaptic strength. We use single unit and field recordings to investigate the experience-dependent neuronal alterations.


Thalamic single unit recording

2. Learning- and stimulation-induced changes of hippocampal spatial representation.
Given that the hippocampus is critical for spatial memory formation, and that its synapses undergo synaptic plasticity, an important question concerns how the functional activity and synaptic alterations in this region relate to one another. Expeience-dependent studies on place field plasticity provide insights of how dynamical place representations underline hippocampal mnemonic functions. Environmental manipulations demonstrate the ability of hippocampal network to discriminate differences in spatial configurations with time. This process of learning is dependent also on non-spatial and goal-related features, revealing the main function of hippocampus – to relate the temporal episodes with their context:

Septal TBS effect on hippocampal place cells

Septal TBS effect on hippocampal place cells (Mamad et al., 2015)


3. Optogenetically-trigerred network connectivity reconfiguration.
The changes in neuronal efficacy known are as long-term synaptic plasticity. My research is following the up-to-date models of synaptic plasticity and their relation to the structural and functional memory processes demonstrated by behavioral and electrophysiological experiments. Our lab aims to describe how neuroplastic mechanisms work together to create network representations of previous experiences. Here, we apply optogenetic activation of hippocampal cell firing in the context of spatial memory formation:

Hippocampal neuronal responses after septal ChAT stimulation

Hippocampal neuronal responses after septal ChAT stimulation (Mamad et al., 2015)


Specific Research Interests

Marian Tsanov publications

Marian Tsanov pictures

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