Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A preference for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. Because the firing of CT afferents strongly correlates with touch pleasantness, the CT pathway has been considered a social-affective sensory pathway. Recently, ablation of the spinothalamic pathway- thought to convey all C-fiber sensations- in patients with cancer pain impaired pain, temperature, and itch, but not ratings of pleasant touch. This suggested integration of afferent A and CT fiber input in the spinal cord, or mechanoreceptive A-fiber contributions to computations of touch pleasantness in the brain. However, contribution of mechanoreceptive A-fibers to touch pleasantness- in humans without pain- remains unknown. In the current, single-blinded study we performed two types of peripheral nerve blocks in healthy adults to temporarily eliminate the con...

Animals are capable of representing different scale spaces from smaller to larger ones. However, most laboratory animals live their life in a narrow range of scale spaces like home-cages and experimental setups, making it hard to extrapolate the spatial representation and learning process in large scale spaces from those in conventional scale spaces. Here, we developed a 3-meter diameter Barnes maze (BM3), then explored whether spatial learning in the Barnes maze (BM) is calibrated by scale spaces. Spatial learning in the BM3 was successfully established with a lower learning rate than that in a conventional 1-meter diameter Barnes maze (BM1). Specifically, analysis of exploration strategies revealed that the mice in the BM3 persistently searched certain places throughout the learning, while such places were rapidly decreased in the BM1. These results suggest dedicated exploration strategies requiring more trial-and-errors and computational resources in the BM3 than in the BM1, leading to a divergence of s...

Although casual drinkers are a majority of the alcohol drinking population, understanding of the long-term effects of chronic exposure to lower levels of alcohol is limited. Chronic exposure to lower doses of ethanol may facilitate the development of alcohol use disorders, potentially due to ethanol effects on reward learning and motivation. Indeed, our previously published findings showed that chronic low-dose ethanol exposure enhanced motivation for sucrose in male, but not female, mice. As the ventral hippocampus (vHPC) is sensitive to disruption by higher doses of chronic ethanol and tracks reward-related information, we hypothesized that this region is impacted by low-dose ethanol and, further, that manipulating vHPC activity would alter reward motivation. In vivo electrophysiological recordings of vHPC population neural activity during progressive ratio testing revealed that vHPC activity was suppressed in the period immediately after reward seeking (lever press) in ethanol-naïve controls, whereas su...

A central question in the field of aging research is to identify the cellular and molecular basis of neuroresilience. One potential candidate is the small GTPase, Rab10. Here we used Rab10+/- mice to investigate the molecular mechanisms underlying Rab10-mediated neuroresilience. Brain expression analysis of 880 genes involved in neurodegeneration showed that Rab10+/- mice have increased activation of pathways associated with neuronal metabolism, structural integrity, neurotransmission, and neuroplasticity compared to their Rab10+/+ littermates. Lower activation was observed for pathways involved in neuroinflammation and aging. We identified and validated several differentially expressed genes (DEGs) including Stx2, Stx1b, Vegfa, Lrrc25 (downregulated); and Prkaa2, Syt4 and Grin2d (upregulated). Behavioral testing showed that Rab10+/- mice perform better in a hippocampal-dependent spatial task (object in place test), while their performance in a classical conditioning task (trace eyeblink conditioning, TECC...

Lateralization of hippocampal function is indicated by varied outcomes of patients with neurological disorders that selectively affect one hemisphere of this structure, such as temporal lobe epilepsy (TLE). The intrahippocampal kainic acid (IHKA) injection model of TLE allows for targeted damage to the left or right hippocampus, enabling systematic comparison of effects of left-right asymmetry on seizure and non-seizure outcomes. Although varying non-seizure phenotypic outcomes based on injection side in dorsal hippocampus were recently evaluated in this model, differences in chronic seizure patterns in left- (IHKA-L) vs. right-injected (IHKA-R) IHKA animals have yet to be evaluated. Here, we assessed hippocampal seizure incidence in male and female IHKA-L and IHKA-R mice. Females displayed increased electrographic seizure activity compared to males at both 2 and 4 months post-injection. In addition, IHKA-L females showed higher seizure frequency than IHKA-R on diestrus and estrus at 2 months post-injectio...

The nucleus accumbens (NAc) is known for its central role in reward and motivation (Day and Carelli, 2007; Floresco, 2015; Salgado and Kaplitt, 2015). Decades of research on the cellular arrangement, density, and connectivity of the NAc have identified two main subregions known as the core and shell (Záborszky et al., 1985; Berendse and Groenewegen, 1990; Zahm and Heimer, 1990). Although anatomically and functionally different, both the NAc core and shell are mainly comprised of GABAergic projection neurons known as MSNs (Matamales et al., 2009). Several studies have identified key morphological differences between core and shell MSNs (Meredith et al., 1992; Forlano and Woolley, 2010) but few studies have directly addressed how core and shell MSNs differ in their intrinsic excitability (Pennartz et al., 1992; O'Donnell and Grace, 1993). Using whole-cell patch clamp recordings in slices prepared from naïve and rewarded male rats, we found that MSNs in the NAc shell were significantly more excitable than MSN...

It is well-known that both hand movements and mental representations of movement lead to event-related desynchronization (ERD) of the electroencephalogram (EEG) recorded over the corresponding cortical motor areas. However, the relationship between ERD in somatosensory cortical areas and mental representations of tactile sensations is not well-understood. In this study, we employed EEG recordings in healthy humans to compare the effects of real and imagined vibrotactile stimulation of the right hand. Both real and imagined sensations produced contralateral ERD patterns, particularly in the μ-band and most significantly in the C3 region. Building on these results and the previous literature, we discuss the role of tactile imagery as part of the complex body image and the potential for using EEG patterns induced by tactile imagery as control signals in brain-computer interfaces (BCIs). Combining this approach with motor imagery could improve the performance of BCIs intended for rehabilitation of sensorimotor...

Transcranial random noise stimulation (tRNS) has been shown to significantly improve visual perception. Previous studies demonstrated that tRNS delivered over cortical areas acutely enhances visual contrast detection of weak stimuli. However, it is currently unknown whether tRNS-induced signal enhancement could be achieved within different neural substrates along the retino-cortical pathway. In 3 experimental sessions, we tested whether tRNS applied to the primary visual cortex(V1) and/or to the retina improves visual contrast detection. We first measured visual contrast detection threshold (VCT; N=24, 16females) during tRNS delivery separately over V1 and over the retina, determined the optimal tRNS intensities for each individual(ind-tRNS), and retested the effects of ind-tRNS within the sessions. We further investigated whether we could reproduce the ind-tRNS-induced modulation on a different session (N=19, 14females). Finally, we tested whether the simultaneous application of ind-tRNS to the retina an...

While animal and human decision strategies are typically explained by model-free and model-based reinforcement learning, their choice sequences often follow simple procedures based on working memory of past actions and rewards. Here we address how working memory-based choice strategies, such as win-stay-lose-switch (WSLS), are represented in the prefrontal and motor cortico-basal ganglia loops by simultaneous recording of neuronal activities in the dorsomedial striatum (DMS), the dorsolateral striatum (DLS), the medial prefrontal cortex (mPFC), and the primary motor cortex (M1). In order to compare neuronal representations when rats employ working memory-based strategies, we developed a new task paradigm, a continuous/intermittent choice task, consisting of choice and no-choice trials. While the continuous condition (CC) consisted of only choice trials, in the intermittent condition (IC), a no-choice trial was inserted after each choice trial to disrupt working memory of the previous choice and reward. Beh...

Brain-derived neurotrophic factor (BDNF) is released from axon terminals originating in the cerebral cortex onto striatal neurons. Here, we characterized BDNF neurons in the corticostriatal circuitry. First, we used BDNF -Cre and Ribotag transgenic mouse lines to label BDNF-positive neurons in the cortex and detected BDNF expression in all the subregions of the prefrontal cortex (PFC). Next, we used a retrograde viral tracing strategy, in combination with BDNF -Cre knock-in mice, to map the cortical outputs of BDNF neurons in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively). We found that BDNF- expressing neurons located in the medial prefrontal cortex (mPFC) project mainly to the DMS, and those located in the primary and secondary motor cortices (M1 and M2, respectively) and agranular insular cortex (AI) project mainly to the DLS. In contrast, BDNF- expressing orbitofrontal cortical (OFC) neurons differentially target the dorsal striatum (DS) depending on their mediolateral and rostro...