GABAA receptors (GABAARs) are crucial components of our brain's communication system. They are involved in controlling the activity of neurons, including striatal spiny projection neurons (SPNs). However, the exact role of GABAARs in synaptic integration, particularly in adult SPNs, remains less understood. In a recent study, researchers employed a range of techniques using MMRRC mice to provide new insights into the complex interactions between GABAARs and another type of receptor, ionotropic glutamate receptors (iGluRs), in regulating neuron function.

To explore the role of GABAARs in adult SPNs, the researchers used a combination of molecular, optogenetic, optical, and electrophysiological approaches on ex vivo brain slices from MMRRC mice. Computational tools were also employed to model somatodendritic synaptic integration, which is the process by which neurons combine multiple signals.

The study found that activating GABAARs caused currents with a reversal potential near -60 mV in both juvenile and adult SPNs. Interestingly, this relatively positive reversal potential was not attributed to the expression of a particular protein (NKCC1), but rather to a balance between two other transporters (KCC2 and Cl-/HCO3-cotransporters).

When researchers activated GABAergic synapses, they observed that SPNs became depolarized from their resting down-state. This GABAAR-mediated depolarization worked together with the stimulation of ionotropic glutamate receptors (iGluRs), leading to increased somatic depolarization and dendritic spikes.

Simulations revealed that a diffuse dendritic GABAergic input to SPNs effectively enhanced the response to coincident glutamatergic input. This finding suggests that GABAARs and iGluRs can work in concert to excite adult SPNs when they are in a resting down-state. The inhibitory role of GABAARs appears to be limited to brief periods near the spike threshold.

The results of this study call for a reevaluation of the role of GABAARs in intrastriatal GABAergic circuits. The discovery that GABAARs can work in conjunction with iGluRs to excite adult SPNs in their resting down-state suggests a more complex role in regulating neuron function than previously thought.

By using MMRRC mice and a variety of techniques, the researchers have provided valuable insights into the intricate interactions between GABAARs and iGluRs in adult brain neurons. This knowledge could potentially lead to a better understanding of various neurological disorders and contribute to the development of more effective treatments.

The study using MMRRC mice has shed light on the complex role of GABAARs in adult striatal spiny projection neurons. By demonstrating that GABAARs can work together with iGluRs to excite adult SPNs in their resting down-state, researchers have opened up new avenues for understanding the regulation of neuronal function and the potential implications for neurological disorders.

Source: https://www.biorxiv.org/content/10.1101/2023.03.14.532627v2