title: GABA inhibition modulates NMDA-R mediated spike timing dependent plasticity (STDP) in a biophysical model.
abstract: Spike timing dependent plasticity (STDP) has been demonstrated in various neural systems of many animals. It has been shown that STDP depends on the target and the location of the synapse and is dynamically regulated by the activity of adjacent synapses, the presence of postsynaptic calcium, presynaptic GABA inhibition or the action of neuromodulators. Recent experimental evidence has reported that the profile of STDP in the CA1 pyramidal neuron can be classified into two types depending on its dendritic location: (1) A symmetric STDP profile in the proximal to the soma dendrites, and (2) an asymmetric one in the distal dendrites. Bicuculline application revealed that GABA(A) is responsible for the symmetry of the STDP curve. We investigate via computer simulations how GABA(A) shapes the STDP profile in the CA1 pyramidal neuron dendrites when it is driven by excitatory spike pairs (doublets). The model constructed uses calcium as the postsynaptic signaling agent for STDP and is shown to be consistent with classical long-term potentiation (LTP) and long-term depression (LTD) induced by several doublet stimulation paradigms in the absence of inhibition. Overall, simulation results provide computational evidence for the first time that the switch between the symmetrical and the asymmetrical STDP operational modes is indeed due to GABA inhibition. Furthermore, gamma frequency inhibition and not theta one is responsible for the transition from asymmetry-to-symmetry. The resulted symmetrical STDP profile is centered at +10 ms with two distinct LTD tails at -10 and +40 ms. Finally, the asymmetry-to-symmetry transition is strongly dependent on the strength (conductance) of inhibition and its relative onset with respect to pre- and postsynaptic spike stimulation.
authors.affiliation: Center for Memory and Brain, Boston University, Boston, MA 02215, USA. vcut@bu.edu
authors.forename: Vassilis
authors.initials: V
authors.lastname: Cutsuridis
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001703:Biophysics; D056547:CA1 Region, Hippocampal / Q000166:cytology; D003198:Computer Simulation; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D008959:Models, Neurological; D009433:Neural Inhibition / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D005680:gamma-Aminobutyric Acid