Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release.

Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small 'extinction burst', further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.

A Wireless IC for Wide-Range Neurochemical Monitoring Using Amperometry and Fast-Scan Cyclic Voltammetry.

An integrated circuit for real-time wireless monitoring of neurochemical activity in the nervous system is described. The chip is capable of conducting measurements in both fast-scan cyclic voltammetry (FSCV) and amperometry modes for a wide input current range. The chip architecture employs a second-order DeltaSigma modulator (DeltaSigmaM) and a frequency-shift-keyed transmitter operating near 433 MHz. It is fabricated using the AMI 0.5-mum double-poly triple-metal n-well CMOS process, and requires only one off-chip component for operation. A measured current resolution of 12 pA at a sampling rate of 100 Hz and 132 pA at a sampling rate of 10 kHz is achieved in amperometry and 300-V/s FSCV modes, respectively, for any input current in the range of plusmn430 nA. The modulator core and the transmitter draw 22 and 400 muA from a 2.6-V power supply, respectively. The chip has been externally interfaced with a carbon-fiber microelectrode implanted acutely in the caudate-putamen of an anesthetized rat, and, for the first time, extracellular levels of dopamine elicited by electrical stimulation of the medial forebrain bundle have been successfully recorded wirelessly using 300-V/s FSCV.