Response properties in primary sensory cortices are highly dependent on behavioral state. For example, the nucleus basalis of the forebrain plays a critical role in enhancing response properties of excitatory neurons in primary visual cortex (V1) during active exploration and learning. Given the strong reciprocal connections between hierarchically arranged cortical regions, how are increases in sensory response gain constrained to prevent runaway excitation? To explore this, we used in vivo two-photon guided cell-attached recording in conjunction with spatially restricted optogenetic photo-inhibition of higher-order visual cortex in mice. We found that the principle feedback projection to V1 originating from the lateral medial area (LM) facilitated visual responses in layer 2/3 excitatory neurons by ϳ20%. This facilitation was reduced by half during basal forebrain activation due to differential response properties between LM and V1. Our results demonstrate that basal-forebrain-mediated increases in response gain are localized to V1 and are not propagated to LM and establish that subcortical modulation of visual cortex is regionally distinct.

Microelectrode arrays (MEAs) provide the means to record electrophysiological activity fundamental to both basic and clinical neuroscience (e.g. brain-computer interfaces). Despite recent advances, current MEAs have significant limitations -including recording density, fragility, expense, and the inability to optimize the probe to individualized study or patient needs.Here we address the technological limitations through the utilization of the newest developments in 3D nanoparticle printing. 1 Our 'CMU Arrays' possess previously impossible electrode densities (> 6000 channels/cm 2 ) with tip diameters as small as 10µm. Most importantly, the probes are entirely customizable owing to the adaptive manufacturing process. Any combination of individual shank lengths, impedances, and layouts are possible. This is achieved in part via our new multi-layer, multi material, custom 3D-printed circuit boards, a fabrication advancement in itself. This device design enables new experimental avenues of targeted, large-scale recording of electrical signals from a variety of biological tissues.

Microelectrode arrays provide the means to record electrophysiological activity critical to brain research. Despite its fundamental role, there are no means to customize electrode layouts to address specific experimental or clinical needs. Moreover, current electrodes demonstrate substantial limitations in coverage, fragility, and expense. Using a 3D nanoparticle printing approach that overcomes these limitations, we demonstrate the first in vivo recordings from electrodes that make use of the flexibility of the 3D printing process. The customizable and physically robust 3D multi-electrode devices feature high electrode densities (2600 channels/cm 2 of footprint) with minimal gross tissue damage and excellent signal-to-noise ratio. This fabrication methodology also allows flexible reconfiguration consisting of different individual shank lengths and layouts, with low overall channel impedances. This is achieved, in part, via custom 3D printed multilayer circuit boards, a fabrication advancement itself that can support several biomedical device possibilities. This effective device design enables both targeted and large-scale recording of electrical signals throughout the brain.

Studies of the neural mechanisms underlying value-based decision making typically employ food or fluid rewards to motivate subjects to perform cognitive tasks. Rewards are often treated as interchangeable, but it is well known that the specific tastes of foods and fluids and the values associated with their taste sensations influence choices and contribute to overall levels of food consumption. Accordingly, we characterized the gustatory system in three macaque monkeys (Macaca mulatta) and examined whether gustatory responses were modulated by preferences and hydration status. To identify taste-responsive cortex, we delivered small quantities (0.1 ml) of sucrose (sweet), citric acid (sour), or distilled water in random order without any predictive cues while scanning monkeys using event-related fMRI. Neural effects were evaluated by using each session in each monkey as a data point in a second-level analysis. By contrasting BOLD responses to sweet and sour tastes with those from distilled water in a group level analysis, we identified taste responses in primary gustatory cortex area G, an adjacent portion of the anterior insular cortex, and prefrontal cortex area 12o. Choice tests administered outside the scanner revealed that all three monkeys strongly preferred sucrose to citric acid or water. BOLD responses in the ventral striatum, ventral pallidum, and amygdala reflected monkeys’ preferences, with greater BOLD responses to sucrose than citric acid. Finally, we examined the influence of hydration level by contrasting BOLD responses to receipt of fluids when monkeys were thirsty and after ad libitum water consumption. BOLD responses in area G and area 12o in the left hemisphere were greater following full hydration. By contrast, BOLD responses in portions of medial frontal cortex were reduced after ad libitum water consumption. These findings highlight brain regions involved in representing taste, taste preference and internal state.