Objective. Multimodal measurements at the neuronal level allow for detailed insight into local circuit function. However, most behavioral studies focus on one or two modalities and are generally limited by the available technology. Approach. Here, we show a combined approach of electrophysiology recordings, chemical sensing, and histological localization of the electrode tips within tissue. The key enabling technology is the underlying use of carbon fiber electrodes, which are small, electrically conductive, and sensitive to dopamine. The carbon fibers were functionalized by coating with Parylene C, a thin insulator with a high dielectric constant, coupled with selective re-exposure of the carbon surface using laser ablation. Main results. We demonstrate the use of this technology by implanting 16 channel arrays in the rat nucleus accumbens. Chronic electrophysiology and dopamine signals were detected 1 month post implant. Additionally, electrodes were left in the tissue, sliced in place during histology, and showed minimal tissue damage. Significance. Our results validate our new technology and methods, which will enable a more comprehensive circuit level understanding of the brain.

Spindles and slow oscillations (SOs) both appear to play an important role in memory consolidation. Spindle and SO "nesting," or the temporal overlap between the two events, is believed to modulate consolidation. However, the neurophysiological processes modified by nesting remain poorly understood. We thus recorded activity from the primary motor cortex of 4 male sleeping rats to investigate how SO and spindles interact to modulate the correlation structure of neural firing. During spindles, primary motor cortex neurons fired at a preferred phase, with neural pairs demonstrating greater neural synchrony, or correlated firing, during spindle peaks. We found a direct relationship between the temporal proximity between SO and spindles, and changes to the distribution of neural correlations; nesting was associated with narrowing of the distribution, with a reduction in low-and high-correlation pairs. Such narrowing may be consistent with greater exploration of neural states. Interestingly, after animals practiced a novel motor task, pairwise correlations increased during nested spindles, consistent with targeted strengthening of functional interactions. These findings may be key mechanisms through which spindle nesting supports memory consolidation.

The strength of cortical connectivity to the striatum influences the balance between behavioral variability and stability. Learning to consistently produce a skilled action requires plasticity in corticostriatal connectivity associated with repeated training of the action. However, it remains unknown whether such corticostriatal plasticity occurs during training itself or 'offline' during time away from training, such as sleep. Here, we monitor the corticostriatal network throughout long-term skill learning in rats and find that non-REM (NREM) sleep is a relevant period for corticostriatal plasticity. We first show that the offline activation of striatal NMDA receptors is required for skill learning. We then show that corticostriatal functional connectivity increases offline, coupled to emerging consistent skilled movements and coupled cross-area neural dynamics. We then identify NREM sleep spindles as uniquely poised to mediate corticostriatal plasticity, through interactions with slow oscillations. Our results provide evidence that sleep shapes cross-area coupling required for skill learning.

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This paper reports on a new structure and fabrication technology for Parylene-based recording and stimulating penetrating microprobes with engineered mechanical stiffness, low cross-sectional area and sharp tips. Taking advantage of significant benefits from polymer microprobes is often prevented due to their troublesome insertion. This paper addresses this issue and describes a process that allows integrating vertical Parylene stiffeners in the shank without adding process complexity, increasing probe thickness and volume or compromising use in 2D/3D arrays. A metal mask formed around the tip allows for the local thinning down of Parylene, creating a sharp tip during an etch step. These features increase the stability of the probe while reducing both the load on the shank during implantation as well as the dimpling of the brain surface. Shanks 2 mm long, 20 µm thick and 380 µm wide were rendered stable enough for insertion into cadaver lamb brain through the pia by employing five stiffeners. Probes were fabricated in a three mask process with high yield (>80%), and under soak-tests it was determined that they remain electrically functional over a period of three months.