The ventral pallidum (VP) is an integral locus in the reward circuitry and a major target of GABAergic innervation of both D1-medium spiny neurons (MSNs) and D2-MSNs from the nucleus accumbens. The VP contains populations of GABAergic [VPGABA, GAD2(+), or VGluT(–)] and glutamatergic [VPGlutamate, GAD2(–), or VGluT(+)] cells that facilitate positive reinforcement and behavioral avoidance, respectively. MSN efferents to the VP exert opponent control over behavioral reinforcement with activation of D1-MSN afferents promoting and D2-MSN afferents inhibiting reward seeking. How this afferent-specific and cell type-specific control of reward seeking is integrated remains largely unknown. In addition to GABA, D1-MSNs corelease substance P to stimulate neurokinin 1 receptors (NK1Rs) and D2-MSNs corelease enkephalin to activate μ-opioid receptors (MORs) and δ-opioid receptors. These neuropeptides act in the VP to alter appetitive behavior and reward seeking. Using a combination of optogenetics and patch-clamp elect...

Highlighted Research Paper: [[L. J. Sukman and E. Stark, “Cortical pyramidal and parvalbumin cells exhibit distinct spatiotemporal extracellular electric potentials.” eNeuro (2022).][2]][2] []: /lookup/doi/10.1523/ENEURO.0265-22.2022

Discriminating between temporal features in sensory stimuli is critical to complex behavior and decision-making. However, how sensory cortical circuit mechanisms contribute to discrimination between subsecond temporal components in sensory events is unclear. To elucidate the mechanistic underpinnings of timing in primary visual cortex (V1), we recorded from V1 using two-photon calcium imaging in awake-behaving mice performing a go/no-go discrimination timing task, which was composed of patterns of subsecond audiovisual stimuli. In both conditions, activity during the early stimulus period was temporally coordinated with the preferred stimulus. However, while network activity increased in the preferred condition, network activity was increasingly suppressed in the nonpreferred condition over the stimulus period. Multiple levels of analyses suggest that discrimination between subsecond intervals that are contained in rhythmic patterns can be accomplished by local neural dynamics in V1.

The striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of the basal ganglia. Projection neurons of both striatum and STN can extensively interact with other basal ganglia nuclei, and there is growing anatomic evidence of direct axonal connections from the STN to striatum. There remains, however, a pressing need to elucidate the organization and impact of these subthalamostriatal projections in the context of the diverse cell types constituting the striatum. To address this, we conducted monosynaptic retrograde tracing from genetically-defined populations of dorsal striatal neurons in adult male and female mice, quantifying the connectivity from STN neurons to spiny projection neurons, GABAergic interneurons, and cholinergic interneurons. In parallel, we used a combination of ex vivo electrophysiology and optogenetics to characterize the responses of a complementary range of dorsal striatal neuron types to activation of STN axons. Our tracing studies showed that the connect...

Neural population dynamics provide a key computational framework for understanding information processing in the sensory, cognitive, and motor functions of the brain. They systematically depict complex neural population activity, dominated by strong temporal dynamics as trajectory geometry in a low-dimensional neural space. However, neural population dynamics are poorly related to the conventional analytical framework of single-neuron activity, the rate-coding regime that analyzes firing rate modulations using task parameters. To link the rate-coding and dynamic models, we developed a variant of state-space analysis in the regression subspace, which describes the temporal structures of neural modulations using continuous and categorical task parameters. In macaque monkeys, using two neural population datasets containing either of two standard task parameters, continuous and categorical, we revealed that neural modulation structures are reliably captured by these task parameters in the regression subspace a...

Speech comprehension is a complex neural process on which relies on activation and integration of multiple brain regions. In the current study, we evaluated whether speech comprehension can be investigated by neural tracking. Neural tracking is the phenomenon in which the brain responses time-lock to the rhythm of specific features in continuous speech. These features can be acoustic, i.e., acoustic tracking, or derived from the content of the speech using language properties, i.e., language tracking. We evaluated whether neural tracking of speech differs between a comprehensible story, an incomprehensible story, and a word list. We evaluated the neural responses to speech of 19 participants (six men). No significant difference regarding acoustic tracking was found. However, significant language tracking was only found for the comprehensible story. The most prominent effect was visible to word surprisal, a language feature at the word level. The neural response to word surprisal showed a prominent negativi...

Highlighted Research Paper: [[M. Dusing, C. L. LaSarge, A. White, L. G. Jerow, C. Gross and S. C. Danzer, “Neurovascular Development in Pten and Tsc2 Mouse Mutants.”][2]][2] []: /lookup/doi/10.1523/ENEURO.0340-22.2023

The brain interprets sensory inputs to guide behavior, but behavior itself disrupts sensory inputs. Perceiving a coherent world while acting in it constitutes active perception. For example, saccadic eye movements displace visual images on the retina and yet the brain perceives visual stability. Because this percept of visual stability has been shown to be influenced by prior expectations, we tested the hypothesis that it is Bayesian. The key prediction was that priors would be used more as sensory uncertainty increases. Humans and rhesus macaques reported whether an image moved during saccades. We manipulated both prior expectations and levels of sensory uncertainty. All psychophysical data were compared with the predictions of Bayesian ideal observer models. We found that humans were Bayesian for continuous judgments. For categorical judgments, however, they were anti-Bayesian: they used their priors less with greater uncertainty. We studied this categorical result further in macaques. The animals’ judgm...

About one-third of individuals living with epilepsy have treatment-resistant seizures. Alternative therapeutic strategies are thus urgently needed. One potential novel treatment target is miRNA-induced silencing, which is differentially regulated in epilepsy. Inhibitors (antagomirs) of specific microRNAs (miRNAs) have shown therapeutic promise in preclinical epilepsy studies; however, these studies were mainly conducted in male rodent models, and research into miRNA regulation in females and by female hormones in epilepsy is scarce. This is problematic because female sex and the menstrual cycle can affect the disease course of epilepsy and may, therefore, also alter the efficacy of potential miRNA-targeted treatments. Here, we used the proconvulsant miRNA miR-324-5p and its target, the potassium channel Kv4.2, as an example to test how miRNA-induced silencing and the efficacy of antagomirs in epilepsy are altered in female mice. We showed that Kv4.2 protein is reduced after seizures in female mice similar ...

Previous diagnostic systems precluded the co-existence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in one person; but, after many clinical reports, the diagnostic criteria were updated to allow their co-occurrence. Despite such a clinical change, the neurobiological bases underpinning the comorbidity remain poorly understood, and whether the ASD+ADHD condition is a simple overlap of the two disorders is unknown. Here, to answer this question, we compared the brain dynamics of high-functioning ASD+ADHD children with age-/sex-/IQ-matched pure ASD, pure ADHD, and typically developing (TD) children. Regarding autistic traits, the socio-communicational symptom of the ASD+ADHD children was explained by the same overstable brain dynamics as seen in pure ASD. In contrast, their ADHD-like traits were grounded on a unique neural mechanism that was unseen in pure ADHD: the core symptoms of pure ADHD were associated with the overly flexible whole-brain dynamics that were trigg...