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Periodic Report Summary 1 - BURSTPAUSEPLASTICITY (Plasticity of the Burst-Pause Response in the Tonically Active Cholinergic Interneurons of the Striatum in Normal and Parkinsonian Mice)

The capacity to redirect attention and assign motivational value to novel stimuli in our ever-changing environment depends on the excitatory (glutamatergic) projection from the parafascicular (PF) nucleus of the thalamus to the striatum. The assignment of value takes the form of a burst-pause (B-P) sequence that interrupts the tonic firing of striatal cholinergic interneurons (ChIs) that are targets of this projection. The B-P response is a neural correlate of classical conditioning, in the sense that its size (eg, the length of the pause) changes with conditioning. The objectives of the current study were i) to characterize the biophysical mechanism underlying the B-P response of ChIs (both in terms of their intrinsic cellular properties and the role of afferent synaptic effect); ii) to determine what cellular adaptations give rise to the plasticity of the B-P response; iii) to study how this plasticity impacts striatal function; iv) to explain the dopamine dependency of the B-P response, and to provide insight into how it can be restored after dopamine depletion.
Our initial observation demonstrated a putative mechanism for the plasticity of the B-P response in the form of the augmentation of the current underlying the slow afterhyperpolarization observed in ChIs. During the first two years of the project we have established and refined two animal models for selective activation of cortical vs. thalamic input to ChIs, respectively. However, this task and replicating the initial finding have proven challenging, and we currently working to overcome or circumvent them by adopting alternative strategies. This work has led to interesting new insights in the differences in synaptic transmission along the cortico - and thalamo-striatal synapses to ChIs, which we are also pursuing. Ultimately, we will also compare these projections in dopamine depleted animals, which could provide valuable new insights into the role of ChIs in Parkinson’s disease.
During the two years since the beginning of the project, I have secured substantial extramural funding for my nascent laboratory, most notably, a 2M Euro ERC Consolidator grant. My group is currently composed of 4 PhDs (postdocs, a lab manager and research associate) and 3 graduate students. I am approaching the halfway point in the tenure process, with a number of manuscripts either published or close to being published in top tiered journals (e.g. J Neurosci).


Hani Ben-Yehuda, (Coordinator for Europe)
Tel.: +972 2 6586676
Fax: +977 7 22447007


Life Sciences
Record Number: 188996 / Last updated on: 2016-09-19
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