The direct and indirect pathways of the basal ganglia (BG) have been suggested to learn mainly from positive and negative feedbacks, respectively. Since these pathways unevenly receive inputs from different cortical neuron types and/or regions, they may preferentially use different state/action representations. We explored whether such a combined use of different representations, coupled with different learning rates from positive and negative reward prediction errors (RPEs), has computational benefits. We modeled animal as an agent equipped with two learning systems, each of which adopted individual representation (IR) or successor representation (SR) of states. With varying the combination of IR or SR and also the learning rates from positive and negative RPEs in each system, we examined how the agent performed in a dynamic reward navigation task. We found that combination of SR-based system learning mainly from positive RPEs and IR-based system learning mainly from negative RPEs could achieve a good per...

The study used machine learning to predict The American Spinal Injury Association Impairment Scale (AIS) scores for newly injured spinal cord injury patients at hospital discharge time from hospital admission data. Additionally, machine learning was used to analyze the best model for feature importance to validate the criticality of the AIS score and highlight relevant demographic details. The data used for training machine learning models was from the National Spinal Cord Injury Statistical Center (NSCISC) database of U.S. spinal cord injury patient details. Eighteen real features were used from 417 provided features, which mapped to 53 machine learning features after processing. Eight models were tuned on the dataset to predict AIS scores, and Shapely analysis was performed to extract the most important of the 53 features. Patients within the NSCISC database who sustained injuries were between 1972 and 2016 after data cleaning ( n  = 20,790). Outcomes were test set multiclass accuracy and aggregated Shap...

Avoiding potentially harmful, and consuming safe food is crucial for the survival of living organisms. However, the perceived valence of sensory information can change following conflicting experiences. Pleasurability and aversiveness are two crucial parameters defining the perceived valence of a taste and can be impacted by novelty. Importantly, the ability of a given taste to serve as the conditioned stimulus (CS) in conditioned taste aversion (CTA) is dependent on its valence. Activity in anterior insula (aIC) Layer IV–VI pyramidal neurons projecting to the basolateral amygdala (BLA) is correlated with and necessary for CTA learning and retrieval, as well as the expression of neophobia toward novel tastants, but not learning taste familiarity. Yet, the cellular mechanisms underlying the updating of taste valence representation in this specific pathway are poorly understood. Here, using retrograde viral tracing and whole-cell patch-clamp electrophysiology in trained mice, we demonstrate that the intrinsi...

A central question in neuroscience is how sensory inputs are transformed into percepts. At this point, it is clear that this process is strongly influenced by prior knowledge of the sensory environment. Bayesian ideal observer models provide a useful link between data and theory that can help researchers evaluate how prior knowledge is represented and integrated with incoming sensory information. However, the statistical prior employed by a Bayesian observer cannot be measured directly, and must instead be inferred from behavioral measurements. Here, we review the general problem of inferring priors from psychophysical data, and the simple solution that follows from assuming a prior that is a Gaussian probability distribution. As our understanding of sensory processing advances, however, there is an increasing need for methods to flexibly recover the shape of Bayesian priors that are not well approximated by elementary functions. To address this issue, we describe a novel approach that applies to arbitrary...

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...

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 ...

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer’s disease (AD) and Parkinson’s disease (PD), respectively. The onset of these pathologies coincides with loss of noradrenergic fibers in LC target regions and the emergence of prodromal symptoms including sleep disturbances and anxiety. Paradoxically, these prodromal symptoms are indicative of a noradrenergic hyperactivity phenotype, rather than the predicted loss of norepinephrine (NE) transmission following LC damage, suggesting the engagement of complex compensatory mechanisms. Because current therapeutic efforts are targeting early disease, interest in the LC has grown, and it is critical to identify the links between pathology and dysfunction. We employed the LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), which preferentially damages LC axons, to model early changes in the LC-NE system pertinent to AD and PD in male and female mice. DSP-4 (two doses of 50 mg/kg...

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...

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...

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...