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...

Tau is a microtubule-associated protein (MAP) that has multiple isoforms generated by alternative splicing of the MAPT gene at a range of 45–60 kDa [low-molecular-weight (LMW) tau] as well as a unique isoform termed Big tau containing an additional exon 4a encoding a large projecting domain of ∼250 aa to form a protein of 110 kDa. Big tau is expressed in adult PNS neurons such as DRG neurons and specific regions of CNS such as the cerebellum in a developmental transition from LMW tau to Big tau during the postnatal period. Despite a conserved size of the 4a exons across the vertebrate phylogeny, there is no sequence homology among different species outside the Mammalia class, which underscores the focus on structural preservation of Big tau. Despite the original discovery of Big tau in the early 1990s, there has been little progress elucidating its physiological properties and pathologic implications. We propose that Big tau may be able to improve axonal transport in projecting axons and speculate on the p...

Arousal powerfully influences cortical activity, in part by modulating local inhibitory circuits. Somatostatin (SOM)-expressing inhibitory interneurons are particularly well situated to shape local population activity in response to shifts in arousal, yet the relationship between arousal state and SOM activity has not been characterized outside of sensory cortex. To determine whether SOM activity is similarly modulated by behavioral state across different levels of the cortical processing hierarchy, we compared the behavioral modulation of SOM-expressing neurons in auditory cortex (AC), a primary sensory region, and posterior parietal cortex (PPC), an association-level region of cortex, in mice. Behavioral state modulated activity differently in AC and PPC. In PPC, transitions to high arousal were accompanied by large increases in activity across the full PPC neural population, especially in SOM neurons. In AC, arousal transitions led to more subtle changes in overall activity, as individual SOM and Non-SO...

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 with 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, and 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 classical ...

Spinal cord stimulation (SCS) evokes fast epidural evoked compound action potential (ECAP) that represent activity of dorsal column axons, but not necessarily a spinal circuit response. Using a multimodal approach, we identified and characterized a delayed and slower potential evoked by SCS that reflects synaptic activity within the spinal cord. Anesthetized female Sprague Dawley rats were implanted with an epidural SCS lead, epidural motor cortex stimulation electrodes, an epidural spinal cord recording lead, an intraspinal penetrating recording electrode array, and intramuscular electromyography (EMG) electrodes in the hindlimb and trunk. We stimulated the motor cortex or the epidural spinal cord and recorded epidural, intraspinal, and EMG responses. SCS pulses produced characteristic propagating ECAPs (composed of P1, N1, and P2 waves with latencies <2 ms) and an additional wave (“S1”) starting after the N2. We verified the S1-wave was not a stimulation artifact and was not a reflection of hindlimb/trun...

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 because of 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-naive controls, wherea...

The nucleus accumbens (NAc) is known for its central role in reward and motivation ([Day and Carelli, 2007][1]; [Floresco, 2015][2]; [Salgado and Kaplitt, 2015][3]). 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][4]; [Berendse and Groenewegen, 1990][5]; [Zahm and Heimer, 1990][6]). Although anatomically and functionally different, both the NAc core and shell are mainly comprised of GABAergic projection neurons known as medium spiny neurons (MSNs) ([Matamales et al., 2009][7]). Several studies have identified key morphologic differences between core and shell MSNs ([Meredith et al., 1992][8]; [Forlano and Woolley, 2010][9]) but few studies have directly addressed how core and shell MSNs differ in their intrinsic excitability ([Pennartz et al., 1992][10]; [O’Donnell and Grace, 1993][11]). Using whole-cell patch-clamp recordings in slices prepared from naive and rewarded male rats, ...

With a wide variety of dopamine transporter (DAT) antibodies available commercially, it is important to validate which antibodies provide sufficient immunodetection for reproducibility purpose and for accurate analysis of DAT levels and/or location. Commercially available DAT antibodies that are commonly used were tested in western blotting (WB) on wild-type (WT) and DAT-knock-out (DAT-KO) brain tissue and with immunohistology (IH) techniques against coronal slices of unilaterally lesioned 6-OHDA rats, in addition to wild-type and DAT-knock-out mice. DAT-KO mice and unilateral 6-OHDA lesions in rats were used as a negative control for DAT antibody specificity. Antibodies were tested at various concentrations and rated based on signal detection varying from no signal to optimal signal detection. Commonly used antibodies, including AB2231 and PT-22 524-1-AP, did not provide specific DAT signals in WB and IH. Although certain antibodies provided a good DAT signal, such as SC-32258, D6944, and MA5-24796, they ...

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 co...

As basic and preclinical scientists, graduate students and trainees emphatically support the importance of both hearing and understanding the perspectives of individuals living with spinal cord injury (SCI); however, it is much more complex than most realize. Establishing avenues of communication among individuals with SCI, caretakers, and/or researchers is paramount to the success of our efforts in becoming well rounded researchers that are knowledgeable about principles of human well being. Here, we discuss the divides between researchers and individuals living with SCI that often create misunderstandings. By expanding on two topics within these divides, we seek to highlight the main message of this commentary from the student perspective: there is a need within the SCI research community for better data-sharing practices and communication among preclinical researchers, clinicians, and individuals living with SCI. First, we will discuss the diversity of data collection and sharing within the research rea...