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Dr Marian Tsanov

Job title
Assistant Professor
Organisation
Trinity College Dublin
Broad research area
Basic Science Research
clinical_research
Research interests
1. Contextual memory trace formation.
A central challenge of fundamental neuroscience is to understand how the brain stores and upgrades memories. The process of encoding and updating contextual information crucially depends on the extended hippocampal formation, where neurons encode a spatial map of the environment. I combine recent methodological advances to provide a causal link between long-term physiological changes across the limbic system and learning behaviour.

2. Aversive and appetitive conditioning behaviour during spatial navigation.
If we ultimately aim to ameliorate the memories of traumatic events for the treatment of posttraumatic stress disorders we need to uncover 1) how the aversive episodes rewire the brain connectivity and 2) how we can manipulate this process. I investigate how glutamatergic ensemble activity in basolateral complex of amygdala relates electrophysiological properties of experience-dependent plasticity and behaviour.

3. Neuromodulation of synaptic plasticity and learning.
Memory consolidation is the phenomenon by which a newly formed memory transitions from a fragile state to a stable, long-term state. The defining feature of consolidation is a finite time window that begins immediately after learning, during which a memory is susceptible to disruptions. I investigate how dopaminergic and cholinergic neuromodulation controls episodic memory consolidation and extinction.

4. 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. I explore the interregional neuronal communication, and how it reflects long-lasting changes in firing neuronal properties between regions.

5. Hippocampo-diencephalic interaction in the formation of episodic-like memory.
I investigate the anatomical and physiological connections between different hierarchical levels of the limbic system across the hippocampo-thalamic and hippocampo-hypothalamic connections. I investigate the properties of head-direction cells during behavioural tasks, which allow us to gain an insight of what information is encoded in the directional signal.

6. Computational investigation of neuronal biophysical properties in the thalamic and septo-hippocampal networks.
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.

7. Chronic activation of cholinergic projections to the episodic memory networks.
Using photostimulation protocols that mimic the spiking activity of septal neurons, I have shown that the modulatory role of septal cholinergic control over the hippcampal place field representation is mediated by the rhythmic entrainment of hippocampal neurons. Recent work in my lab showed that the place cells are not simply coincidence detectors but they actively mediate the learning between context and location and this process is regulated by the dopaminergic neuromoudulator inputs. My next research aims target the investigation of cholinergic optogenetic and pharmacological control of neuromodulation in aged animals and Alzheimer model animals.

8. Chronic control of cholinergic and dopaminergic cross-talk in the limbic circuitry.
Memory consolidation is the phenomenon by which a newly formed memory transitions from a fragile state to a stable, long-term state. Hippocampus temporally encodes representations of spatial context-dependent experiences and these memory traces are functionally strengthened in the cortical areas for long-term recollection. The defining feature of consolidation is a finite time window that begins immediately after learning, during which a memory is susceptible to disruptions, such as protein synthesis inhibition, resulting in retrograde amnesia. I plan to apply the engram methodology to the test the network substrate for episodic memory consolidation and retrograde amnesia. My subsequent research aims target the investigation of dopaminergic optogenetic and pharmacological control of neuromodulation in animal model of depression.

9. Interrogation of the circuits mediating both amnesic and depressive dysfunction.
If we ultimately aim to enhance the memories for declarative events for the treatment of neurodegenerative we need to uncover 1) how the context-dependent episodes rewire the brain connectivity and 2) how we can manipulate this process. Current theories propose that memory of an event is represented by a population of neurons, referred to as engram. Engrams engage overlapping neuronal populations for different memories, such as the encoding of a single spatial environment with differing contextual emotional valences. Despite recent advances in localizing and manipulating single engrams, it is still unclear which neurons remap to encode fearful experience and which neurons preserve their spatial fields. I have recently examined the rules governing aversion-induced place field remapping. We showed that the place cells remapping follows spatial and temporal pattern, which depends on the aversive stimulus perception.

10. Translation of neuroscience in neurology.
Recent progress in neuroscience techniques will allow us to translate the fundamental neuroscience knowledge into applications that treat neurocognitive disorders. Experiments performed so far only in vitro are now able to be tested in freely behaving animals, where we could relate neuronal communication to cognitive processes. The convergence between neuromodulatory models and behavioral research is finally possible due to 1) major advances in long-term multiple units recordings, 2) tremendous growth of anatomical and physiological data about episodic memory circuits, 3) recent development of the biological and computational tools for the evaluation of the signal processing in vivo and in silico. My research brings all three areas into focus, enabling our aim to describe how neuromodulatory mechanisms work together to augment network representations of previous experiences for the treatment of neurodegenerative diseases.
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