Inhibitory contribution to suprathreshold corticostriatal responses: an experimental and modeling study

Area of Science:

• Neuroscience
• Computational Neuroscience
• Synaptic Plasticity

Background:

• Neostriatal neurons exhibit spontaneous synchronization, despite being primarily inhibitory.
• This synchronization is not fully explained by existing models of excitatory networks.
• Plateau-like depolarizations, or up-states, in medium spiny neurons (MSNs) are key to this synchronization.

Purpose of the Study:

• To investigate the role of asynchronous shunting GABAergic inputs in sustaining plateau potentials in MSNs.
• To understand how the neostriatum achieves autonomous processing with tonic excitation and independent inputs.
• To explore the contribution of inhibitory synapses to sustained neuronal activity.

Main Methods:

• Experimental induction of plateau-like depolarizations in MSNs using corticostriatal stimuli.
• Analysis of synaptic currents, including AMPA/KA, NMDA, and intrinsic Ca2+ currents.
• Utilized a NEURON computational model of spiny cells to simulate synaptic input effects.

Main Results:

• Inhibitory synapses contribute to maintaining slow depolarization, alongside excitatory and intrinsic currents.
• While initially depressing firing, inhibitory synapses play a crucial role in sustaining the plateau response.
• Asynchronous inhibitory inputs on dendrites can successfully simulate experimentally observed plateau potentials.

Conclusions:

• Asynchronous inhibitory inputs are critical for sustaining plateau potentials in neostriatal neurons.
• This mechanism helps explain autonomous processing within the striatal micro-circuitry.
• The findings highlight a novel role for inhibitory synapses in network dynamics beyond simple inhibition.