When two sufficiently different stimuli are presented to each eye, perception alternates between them. This binocular rivalry is conceived as a competition for representation in the single stream of visual consciousness. The magnocellular (M) and parvocellular (P) pathways, originating in the retina, encode disparate information, but their potentially different contributions to binocular rivalry have not been determined. Here, we used functional magnetic resonance imaging to measure the human lateral geniculate nucleus (LGN), where the M and P neurons are segregated into layers receiving input from a single eye. We had three participants (one male, two females) and used achromatic stimuli to avoid contributions from color opponent neurons that may have confounded previous studies. We observed activity in the eye-specific regions of LGN correlated with perception, with similar magnitudes during rivalry or physical stimuli alternations, also similar in the M and P regions. These results suggest that LGN acti...

Postsynaptic scaffolding proteins function as central organization hubs, ensuring the synaptic localization of neurotransmitter receptors, trans-synaptic adhesion proteins, and signaling molecules. Gephyrin is the major postsynaptic scaffolding protein at glycinergic and a subset of GABAergic inhibitory synapses. In contrast to cells outside the CNS, where one gephyrin isoform is predominantly expressed, neurons express different splice variants. In this study, we characterized the expression and scaffolding of neuronal gephyrin isoforms differing in the inclusion of the C4 cassettes located in the central C-domain. In hippocampal and cortical neuronal populations, gephyrin P1, lacking additional cassettes, is the most abundantly expressed isoform. In addition, alternative splicing generated isoforms carrying predominantly C4a, and minor amounts of C4c or C4d cassettes. We detected no striking difference in C4 isoform expression between different neuron types and a single neuron can likely express all C4 i...

Environmental enrichment (EE) is beneficial for brain development and function, but our understanding of its capacity to drive circuit repair, the underlying mechanisms, and how this might vary with age remains limited. Ten-m3 knock-out (KO) mice exhibit a dramatic and stereotyped mistargeting of ipsilateral retinal inputs to the thalamus, resulting in visual deficits. We have recently shown a previously unexpected capacity for EE during early postnatal life (from birth for six weeks) to drive the partial elimination of miswired axonal projections, along with a recovery of visually mediated behavior, but the timeline of this repair was unclear. Here, we reveal that with just 3.5 weeks of EE from birth, Ten-m3 KOs exhibit a partial behavioral rescue, accompanied by pruning of the most profoundly miswired retinogeniculate terminals. Analysis suggests that the pruning is underway at this time point, providing an ideal opportunity to probe potential mechanisms. With the shorter EE-period, we found a localized ...

Inhibitory interneurons are important for neuronal circuit function. They regulate sensory inputs and enhance output discriminability ([Olsen and Wilson, 2008][1]; [Root et al., 2008][2]; [Olsen et al., 2010][3]). Often, the identities of interneurons can be determined by location and morphology, which can have implications for their functions ([Wachowiak and Shipley, 2006][4]). While most interneurons fire traditional action potentials, many are nonspiking. These can be seen in insect olfaction ([Laurent and Davidowitz, 1994][5]; [Husch et al., 2009][6]; [Tabuchi et al., 2015][7]) and the vertebrate retina ([Gleason et al., 1993][8]). Here, we present the novel observation of nonspiking inhibitory interneurons in the antennal lobe (AL) of the adult fruit fly, Drosophila melanogaster . These neurons have a morphology where they innervate a patchwork of glomeruli. We used electrophysiology to determine whether their nonspiking characteristic is because of a lack of sodium current. We then used immunohistoch...

Midbrain dopaminergic (DAergic) neurons of the ventral tegmental area (VTA) are engaged by rewarding stimuli and encode reward prediction error to update goal-directed learning. However, recent data indicate that VTA DAergic neurons are functionally heterogeneous with emerging roles in aversive signaling, salience, and novelty, based in part on anatomic location and projection, highlighting a need to functionally characterize the repertoire of VTA DAergic efferents in motivated behavior. Previous work identifying a mesointerpeduncular circuit consisting of VTA DAergic neurons projecting to the interpeduncular nucleus (IPN), a midbrain area implicated in aversion, anxiety-like behavior, and familiarity, has recently come into question. To verify the existence of this circuit, we combined presynaptic targeted and retrograde viral tracing in the dopamine transporter-Cre mouse line. Consistent with previous reports, synaptic tracing revealed that axon terminals from the VTA innervate the caudal IPN; whereas, r...

Altered decision making at advanced ages can have a significant impact on an individual’s quality of life and the ability to maintain personal independence. Relative to young adults, older adults make less impulsive and less risky choices; although these changes in decision making could be considered beneficial, they can also lead to choices with potentially negative consequences (e.g., avoidance of medical procedures). Rodent models of decision making have been invaluable for dissecting cognitive and neurobiological mechanisms that contribute to age-related changes in decision making, but they have predominantly used costs related to timing or probability of reward delivery and have not considered other equally important costs, such as the risk of adverse consequences. The current study therefore used a rat model of decision making involving risk of explicit punishment to examine age-related changes in this form of choice behavior in male rats, and to identify potential cognitive and neurobiological mecha...

We examined the effect of neonatal deafening on frequency-specific pathways for processing of interaural time differences (ITDs) in cochlear-implant stimuli. Animal studies have demonstrated differences in neural ITD sensitivity in the inferior colliculus (IC) depending on the intracochlear location of intracochlear stimulating electrodes. We used neonatally deafened (ND) rats of both sexes and recorded the responses of single neurons in the IC to electrical stimuli with ITDs delivered to the apical or basal cochlea and compared them with acutely deafened (AD) rats of both sexes with normal hearing (NH) during development. We found that neonatal deafness significantly impacted the ITD sensitivity and the ITD tuning patterns restricted to apically driven IC neurons. In ND rats, the ITD sensitivity of apically driven neurons is reduced to values similar to basally driven neurons. The prevalence of ITD-sensitive apical neurons with a peak-shaped ITD tuning curve, which may reflect predominant input from the m...

Huntington disease (HD), caused by dominantly inherited expansions of a CAG repeat results in characteristic motor dysfunction. Although gross motor defects have been extensively characterized in multiple HD mouse models using tasks such as rotarod and beam walking, less is known about forelimb deficits. We develop a high-throughput alternating reward/nonreward water-reaching task and training protocol conducted daily over approximately two months to simultaneously monitor forelimb impairment and mesoscale cortical changes in GCaMP activity, comparing female zQ175 (HD) and wild-type (WT) littermate mice, starting at ∼5.5 months. Behavioral analysis of the water-reaching task reveals that HD mice, despite learning the water-reaching task as proficiently as wild-type mice, take longer to learn the alternating event sequence as evident by impulsive (noncued) reaches and initially display reduced cortical activity associated with successful reaches. At this age gross motor defects determined by tapered beam as...

Down syndrome cell adhesion molecule ( DSCAM ) is located on human chromosome 21 and triplicated in Down syndrome. DSCAM encodes an Ig superfamily cell surface receptor found in both vertebrates and invertebrates. Alternative splicing is more widespread in mammals compared with invertebrates, but Drosophila Dscam1 is remarkably more complex in this respect than its human counterpart. However, both vertebrate and invertebrate DSCAM/Dscam share a similar critical function—neural wiring (Schmucker and Chen, 2009). To create both the accuracy and complexity of neural wiring, one of the indispensable characteristics of neurons is the ability to express a wide repertoire of cell surface receptors. This ensures both specificity and selectivity. Drosophila Dscam1 is one such extraordinary example. Dscam1 undergoes alternative splicing to generate ∼38,000 receptor isoforms. Dscam1 protein has an intracellular C terminus, a transmembrane domain, and an ectodomain with 10 Ig domains and 6 fibronectin type III repeat...

Interoceptive awareness, an awareness of the internal body state, guides adaptive behavior by providing ongoing information on body signals, such as heart rate and energy status. However, it is still unclear how interoceptive awareness of different body organs are represented in the human brain. Hence, we directly compared the neural activations accompanying attention to cardiac (related to heartbeat) and gastric (related to stomach) sensations, which generate cardiac and gastric interoceptive awareness, in the same population (healthy humans, N  = 31). Participants were asked to direct their attention toward heart and stomach sensations and become aware of them in a magnetic resonance imaging (MRI) scanner. The results indicated that the neural activations underlying gastric attention encompassed larger brain regions, including the occipitotemporal visual cortices, bilateral primary motor cortices, primary somatosensory cortex, left orbitofrontal cortex, and hippocampal regions. Cardiac attention, however...