Bieber, Allan

Abstract Although dopamine is commonly studied for its role in incentive motivation, cognition, and various neuropsychiatric disorders, evidence from Parkinson's disease (PD) patients that present auditory deficits suggest that dopamine is also involved in central auditory processing. It has been recently discovered that the subparafascicular thalamic nucleus (SPF) sends dopaminergic projections to the inferior colliculus (IC), an important convergence hub for the ascending and descending auditory pathways. In the present study, our aim was to provide neurochemical evidence that activation of SPF neurons evokes dopamine release in the IC of anesthetized rats using fast‐scan cyclic and paired pulse voltammetry in combination with carbon fiber microelectrodes. Electrical stimulation of the SPF (60 and 90 Hz) evoked dopamine release in the IC in a frequency‐dependent manner, with higher frequencies evoking greater amplitude dopamine responses. Optogenetic‐evoked dopamine responses were similar to the effects of electrical stimulation suggesting that electrical stimulation‐evoked dopamine release was not due to nonspecific activation of fibers of passage, but rather to activation of SPF cells projecting to the IC. Selective dopamine reuptake blockade enhanced the evoked dopamine response, while selective blockade of serotonin did not, confirming the selectivity of the neurochemical recordings to dopamine. Therefore, the SPF neuronal pathway functionally mediates dopamine release in the IC and thus may be involved in auditory processing deficits associated with PD.

OBJECT Despite a promising outlook, existing intraspinal microstimulation (ISMS) techniques for restoring functional motor control after spinal cord injury are not yet suitable for use outside a controlled laboratory environment. Thus, successful application of ISMS therapy in humans will require the use of versatile chronic neurostimulation systems. The objective of this study was to establish proof of principle for wireless control of ISMS to evoke controlled motor function in a rodent model of complete spinal cord injury. METHODS The lumbar spinal cord in each of 17 fully anesthetized Sprague-Dawley rats was stimulated via ISMS electrodes to evoke hindlimb function. Nine subjects underwent complete surgical transection of the spinal cord at the T-4 level 7 days before stimulation. Targeting for both groups (spinalized and control) was performed under visual inspection via dorsal spinal cord landmarks such as the dorsal root entry zone and the dorsal median fissure. Teflon-insulated stimulating platinum-iridium microwire electrodes (50 μm in diameter, with a 30- to 60-μm exposed tip) were implanted within the ventral gray matter to an approximate depth of 1.8 mm. Electrode implantation was performed using a free-hand delivery technique (n = 12) or a Kopf spinal frame system (n = 5) to compare the efficacy of these 2 commonly used targeting techniques. Stimulation was controlled remotely using a wireless neurostimulation control system. Hindlimb movements evoked by stimulation were tracked via kinematic markers placed on the hips, knees, ankles, and paws. Postmortem fixation and staining of the spinal cord tissue were conducted to determine the final positions of the stimulating electrodes within the spinal cord tissue. RESULTS The results show that wireless ISMS was capable of evoking controlled and sustained activation of ankle, knee, and hip muscles in 90% of the spinalized rats (n = 9) and 100% of the healthy control rats (n = 8). No functional differences between movements evoked by either of the 2 targeting techniques were revealed. However, frame-based targeting required fewer electrode penetrations to evoke target movements. CONCLUSIONS Clinical restoration of functional movement via ISMS remains a distant goal. However, the technology presented herein represents the first step toward restoring functional independence for individuals with chronic spinal cord injury.