Synapse – Neurophysiology Suite

Abstract Restoring somatosensory feedback is essential for achieving natural, embodied control of prosthetic limbs. Intracortical microstimulation (ICMS) of the somatosensory cortex can provide artificial touch by activating cortical neurons directly. Here, we systematically investigate how electrode contact size influences amplitude discrimination performance during ICMS. Six rats were chronically implanted with custom multielectrode shanks in the somatosensory cortex. Over twelve weeks, behavioral just-noticeable differences (JNDs) were quantified across eight electrode diameters (5–50 µm) using an adaptive discrimination paradigm. Discrimination thresholds were significantly lower for 5 µm and 10 µm sites than for larger contacts because these electrodes operated at lower reference stimulation amplitudes within their established charge injection safety limits. Weber fractions remained stable across electrode sizes, demonstrating proportional scaling of perceptual sensitivity with stimulus intensity. We used a biophysically realistic modeling framework to identify the underlying neural correlates of ICMS-induced amplitude discrimination. Both the magnitude of neural responses (changes in the number of activated neurons and the total population spike count) and the population mean spike count contributed to perceptual discrimination. These findings indicate that ultra-microelectrodes enable ICMS at substantially lower reference amplitudes, producing lower absolute discrimination thresholds while preserving Weber-like proportional scaling. Ultra-microelectrodes therefore preserve established psychophysical scaling while supporting low-threshold stimulation within their safe charge injection limits, enabling high-density sensory neuroprostheses.

The ventral pallidum (VP) is necessary for reward processing and a key node in dopamine (DA) pathways. Yet the direct DA inputs have not been studied during reward learning. Here, we elucidate the role of VP DA in reward processing using circuit tracing, fibre photometry, and behavioural pharmacology in male rats. We show that VP receives both non-DA and DA inputs from the midbrain. During an instrumental reward conditioning paradigm, we characterized VP DA activity using a DA sensor (GRAB_DA1h) across learning, extinction, re-acquisition, and motivational test. Followed by pharmacological manipulation using the DA-antagonist (fluphenazine) in VP to demonstrate a causal role in reward learning and motivation. Together our findings advance the functional contributions of non-canonical mesolimbic DA pathways.

Background Animals strongly defend protein intake, but how protein status shapes moment-to-moment reward signalling in mesolimbic circuits remains unclear, particularly when the effort required to obtain food varies. Objective We tested whether dietary protein restriction altered nucleus accumbens (NAc) core dopamine signalling when mice worked for food of differing nutritional value in the home cage. Methods Under surgical anaesthesia, male C57BL/6 mice (n=12; ∼12 weeks old at diet initiation) were injected in the NAc core with a virus expressing the fluorescent dopamine sensor GRABDA and implanted with fibre-optic cannulas. In food-access tasks, nose pokes delivered either chow (protein-containing) or sucrose pellets. Across sessions, pellets required either one nose poke (FixedRatio1) or an increasing number (ProgRatio). Fibre photometry measured dopamine release for both pellet types and schedules during three dietary phases: non-restricted diet (NR1; 18% protein), protein-restricted diet (PR; 4%), and restored non-restricted diet (NR2), with 1 week of adaptation between phases. Behavioural and photometry data were analysed using repeated-measures ANOVA. Results Home-cage food intake remained stable, but bodyweight gain fell markedly during PR and partially recovered in NR2 (+10.1% NR1 vs. +1.2% PR vs. +6.0% NR2, p .05). During ProgRatio, dopamine responses at pellet delivery and retrieval did not differ between pellet types in any phase (all ps>.05). Conclusions Protein restriction did not globally amplify reward-related behaviour or dopamine signalling. Instead, it selectively biased NAc dopamine according to the animal's nutritional status, nutrient context, and task demands.