Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task

Abstract

Basal ganglia striosomes, or patches, are rich in mu opioid receptors (MOR) and form a 3-dimiensional labyrinth of cells that extend throughout the mid and anterior striatum in mice. Though previous studies have suggested that striosomes could affect drug-induced motor output in rodents, the functional role of these compartmentalized MOR-rich striosomes is not well understood. To investigate any relationship between the striosomes and motor behavior we used the toxin dermorphin-saporin (DS) to selectively ablate MOR-rich striosomal cells. FVB mice were bilaterally infused with DS in the mid striatum alone or in the mid and anterior striatum, and were tested on three motor tasks and in an open field. Two volume measurement procedures and stereological cell counts were used to confirm the induced pathology. Mice that received DS injections showed significantly smaller volumes (−26 to −44%) and fewer cells (−30 to −49%) in the striosome compartment compared to mice that received control injections of saline or saporin. Striosome pathology was greatest in the dorsolateral striatum. The extrastriosomal matrix was not significantly affected, resulting in an imbalance in the ratio of striosome-to-matrix cells. Behaviorally, toxin injections caused deficits on an accelerating rotarod task and the deficit was worse in mice that received mid and anterior injections than those that received mid striatal injections alone. However, DS-injected mice did not differ from control mice on other motor tasks. We conclude that the MORrich cells of the striosomes are necessary for optimal rotarod performance, including learning and/ or improvement on the task.

Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors

“…Thus, patch and matrix compartments are proposed to operate as independent and functionally separate microcircuits with distinct inputs, local circuitry, and outputs. These anatomical relationships are consistent with the implication of patches in experience-based locomotor learning and reward-guided behavior (Canales and Graybiel, 2000; Friedman et al, 2015; Lawhorn et al, 2009; White and Hiroi, 1998). …”

Striatal patch compartment lesions reduce stereotypy following repeated cocaine administration

“…However, our group and others have previously shown that both the matrix compartment and cholinergic interneurons were unaffected following DERM-SAP treatment (Lawhorn et al, 2009; Murray et al, 2014). In addition, following DERM-SAP treatment, roughly 30% of mu opioid receptor-labeled patches remained intact, which could explain why there was not a complete abolishment of stereotypy following repeated COC treatment and challenge.…”

“…In order to address the role of the patch compartment of rostral striatum in the expression of stereotypy following repeated COC treatment, we utilized the neurotoxin dermorphin-saporin (DERM-SAP (Lawhorn et al, 2009; Murray et al, 2014; Tokuno et al, 2002); to specifically ablate the neurons that comprise the rostral patch compartment prior to exposure to COC. Mu opioid receptors are densely expressed by the neurons of the patch compartment, while the neurons of the matrix compartment contain relatively few mu opioid receptors (Herkenham and Pert, 1981; Pert et al, 1976; Tempel and Zukin, 1987).…”

Genetic-Based Dissection Unveils the Inputs and Outputs of Striatal Patch and Matrix Compartments

“…While the function of the patch and matrix compartments has not been clearly determined, studies suggest roles in motor learning (Canales and Graybiel, 2000; Lawhorn et al, 2009), reward-guided learning (White and Hiroi, 1998) and biasing decisions during cost-benefit conflict (Friedman et al, 2015). Furthermore, patch/matrix are differentially affected in neurological pathologies such as Parkinson’s disease (Koizumi et al, 2013), Huntington’s disease (Lawhorn et al, 2008), drug addiction (Hurd and Herkenham, 1993), and others (Crittenden and Graybiel, 2011).…”