Patch and matrix compartments are known to express different biochemical markers but the causes and consequences of this are not well understood. Furthermore, it is known that both compartments contribute to the direct and indirect output pathways of the striatum. Therefore, the functional consequences of patch-matrix compartmentalization are of interest in understanding local basal ganglia circuitry. In 2015 Dr. Banghart et al. published a paper titled “Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors” which revealed the role of the neuromodulator enkephalin (enk) on patch output in dorsal striatum. Enkephalin is involved in the body’s response to harmful stimuli and is expressed in striatal neurons across species. In humans, enk-expressing striatal projection neurons (SPNs) are part of the indirect pathway of basal ganglia circuitry, while neurons of the direct pathway express other signaling molecules. Importantly, striatal patches are known have a high level of mu opioid receptor (MOR) which binds enk, whereas enk itself is expressed in indirect pathway SPNs (iSPNS) in the matrix. Given clear enk and MORs distribution, it was hypothesized that enk signaling may represent a means of communication between compartments.
In order to study enk signaling, the researchers used a transgenic mouse line allowing for the immunohistochemical identification of both direct and indirect striatal pathways as well as matrix and patch compartments, and performed histochemical and electrophysiological techniques on brain slices. The group recorded synaptic currents in patches while electrically stimulating in patch and then matrix compartments, finding that matrix stimulation did not elicit responses in patches. This observation suggests that patches are synaptically isolated. The most important finding was that enk was shown to modulate inhibitory activity of direct SPNs (dSPN) (see figure below). By expressing channelrhodopsin in both indirect and direct SPNs and examining the effect of enk on optogenetically-evoked inhibitory post-synaptic currents (IPSCs) in both striatal neuron classes, they were able to observe strong suppression by enk of synaptic inhibition originating from iSPNs and weaker suppression on inhibition from dSPNs. Contrary to their hypothesis, it was found that the majority of iSPN modulation on inhibitory activity was mediated by delta opioid receptors (DORs), not MORs. In sum, matrix neurons release enk, which binds predominantly to DORs on iSPN neurons in patches, and these provide collateral input to patch dSPN neurons. The implications of this work are that at least one type of neuromodulator, enkephalin, is a mechanism for patch-matrix communication, potentially gating information flow in the striatum by activating patch-specific DORs.
Written by Emma Boyd, a 1st year in the Neurosciences Graduate Program at UCSD.