Project Details
Projekt
Subcellular distribution and dynamics of neurotransmitter receptors and Cav channels in interneuron plasticity
Applicant
Privatdozent Dr. Akos Kulik
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2014 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 245861656
Physiological bouts of neuronal activity can induce persistent changes in the surface expression level and/or pharmacological, as well as biophysical properties of various neurotransmitter receptors and ion channels in the somato-dendritic and axonal membranes of cortical principal cells (PCs) and GABAergic inhibitory interneurons (INs). Long-term synaptic plasticity at glutamatergic inputs onto INs and at their output synapses has attracted high attention in recent neuroscience research, because of their crucial role in memory formation and learning-related behaviour. Indeed, a high diversity of conditions and forms of IN plasticity has been identified suggesting the involvement of various underlying molecular and cellular mechanisms. Among these processes, the intracellular concentration of Ca2+ has been suggested to be a critical parameter for synaptic plasticity that can be regulated by a plethora of proteins including metabotropic glutamate receptors (mGluRs) and GABAB receptors (GABABRs), ionotropic AMPA-type glutamate receptors (AMPARs), as well as high voltage-activated Ca2+ (Cav) channels. Therefore, we aim to study plasticity-mediated changes in the distribution and density of these key interacting signalling proteins, their spatial relationship at dendritic and axonal compartments of perisomatic-inhibitory parvalbumin-expressing interneurons (PVIs) and dendritic-inhibitory somatostatin-positive interneurons (SOMIs), as well as the activity-dependent structural changes of their terminals using a combination of pharmacological, behavioural and quantitative immunoelectron microscopic approaches. In the last funding period, we learnt that the dendritic localization of mGluR1, Cav channels and GABABRs is dynamically regulated in SOMI dendrites suggesting that (i) their surface density is tightly controlled, and that (ii) there is a crosstalk between these molecules. Here we aim to further address (1) the dynamic regulation of the dendritic distribution and density of AMPARs relative to mGluRs1/5, as well as (2) the activity-dependent (2a) structural and (2b) molecular changes, focusing on the subcellular organization and dynamics of Cav2.1 (P/Q-type) Ca2+ channels and their interacting receptor partners, mGluR7 and GABABRs, in axon terminals of SOMIs and PVIs in the dentate gyrus (DG), the hippocampal subarea CA and primary motor cortex (M1) of mice that have been exposed to brain region-related learning behaviour by our collaborative Research Unit (RU) members. We expect that these investigations will provide insight into the subcellular organization of these functionally interacting receptors and ion channels and reveal how changes in their spatial localization may contribute to the induction and expression of synaptic plasticity in cortical GABAergic cells.
DFG Programme
Research Units
