Dopamine dynamics and cocaine sensitivity differ between striosome and matrix compartments of the striatum

Abstract

The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine-related neurological disorders including Parkinson’s disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. We further demonstrate that this difference is not due to differences in inhibition of dopamine release by dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine enhanced extracellular dopamine in striosomes to a greater degree than in the matrix and concomitantly inhibited dopamine uptake in the matrix to a greater degree than in striosomes. Importantly, these compartment differences in cocaine sensitivity were limited to the dorsal striatum. These findings demonstrate a level of exquisite microanatomical regulation of dopamine by the DAT in striosomes relative to the matrix.

Subcellular probes for neurochemical recording from multiple brain sites

“…As the CF sensing interfaces comprise identical surfaces to traditional CFM sensors (same CF material), observed dopamine sensitivity (2–50 nA/μM) ( ESI † , Fig. S2) is within range of prior work 3,4,9,15,17,18,32,19–21,31 .…”

“…CFM sensors have realized prevalent implementation in analyzing the mechanisms of dopamine signaling and its function in our everyday behavior and in pathology 10,17–19 . Considerable studies have further attempted to investigate the spatial diversity of dopamine neurotransmission in the striatum using the CFM sensor 3,4,17,20,21 . These single channel investigations, however, are limited by the inability to reproduce precisely dopamine measurements at specific brain sites, as they require serial repositioning of the sensor and/or impractical numbers of specimens to assess dopamine heterogeneity.…”

“…Simple lift-off or etching processes were used to bare a discrete length of CF from its parylene encapsulation for a larger electrochemical sensing surface area. As the bared CF sensing elements are of the same geometries and materials to those used in conventional CFM sensors, the sensitivities attained are equivalent to the well-established sensors 3,4,10,17–21 . Batch fabrication methods enable high-yield (8 probes per array and 10 arrays per batch) and reproducible construction of arrays with well-defined pitch (250 μm), lengths (up to 6 mm), and exposed CF sensor length (50–200 μm).…”

Striosome–dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons

“…Dopamine release and activity in the striosomes and matrix are differentially regulated, including by psychomotor stimulants (31,(51)(52)(53); whether such control is related to input from the dopamine cell clusters and dendrons of the bouquets remains to be investigated.…”

Maladaptive Synaptic Plasticity in L-DOPA-Induced Dyskinesia

“…A recent article shows that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. In the VS (ventral lateral striatum and nucleus accumbens), dopamine release in striosomes is greater than in the proximal matrix region, and in the DS (medial and lateral), the opposite is true (Salinas et al, 2016). A recent study reveals that neuromodulator substance P acting through neurokinin-1 receptor (NK1Rs) can boost DA release within the centers of striosomes, but diminish DA release in a border region where striosomes and matrix interface (Brimblecombe and Cragg, 2015).…”