Generation and validation of a D1 dopamine receptor Flpo knock-in mouse.

Background: Dopamine is a powerful neuromodulator of diverse brain functions, including movement, motivation, reward, and cognition. D1-type dopamine receptors (D1DRs) are the most prevalently expressed dopamine receptors in the brain. Neurons expressing D1DRs are heterogeneous and involve several subpopulations.

Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact.

Autism spectrum disorders (ASD) involve brain wide abnormalities that contribute to a constellation of symptoms including behavioral inflexibility, cognitive dysfunction, learning impairments, altered social interactions, and perceptive time difficulties. Although a single genetic variation does not cause ASD, genetic variations such as one involving a non-canonical Wnt signaling gene, Prickle2, has been found in individuals with ASD. Previous work looking into phenotypes of Prickle2 knock-out (Prickle2) and heterozygous mice (Prickle2) suggest patterns of behavior similar to individuals with ASD including altered social interaction and behavioral inflexibility.

Complementary cognitive roles for D2-MSNs and D1-MSNs during interval timing.

The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds and involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2-dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway.

Collateralizing ventral subiculum melanocortin 4 receptor circuits regulate energy balance and food motivation.

Hippocampal dysfunction is associated with major depressive disorder, a serious mental illness characterized by not only depressed mood but also appetite disturbance and dysregulated body weight. However, the underlying mechanisms by which hippocampal circuits regulate metabolic homeostasis remain incompletely understood. Here we show that collateralizing melanocortin 4 receptor (MC4R) circuits in the ventral subiculum (vSUB), one of the major output structures of the hippocampal formation, affect food motivation and energy balance.

Phase-adaptive brain stimulation of striatal D1 medium spiny neurons in dopamine-depleted mice.

Brain rhythms are strongly linked with behavior, and abnormal rhythms can signify pathophysiology. For instance, the basal ganglia exhibit a wide range of low-frequency oscillations during movement, but pathological "beta" rhythms at ~ 20 Hz have been observed in Parkinson's disease (PD) and in PD animal models. All brain rhythms have a frequency, which describes how often they oscillate, and a phase, which describes the precise time that peaks and troughs of brain rhythms occur.

COVID-19 Case Fatality and Alzheimer's Disease.

Previous studies have identified dementia as a risk factor for death from coronavirus disease 2019 (COVID-19). However, it is unclear whether Alzheimer's disease (AD) is an independent risk factor for COVID-19 case fatality rate. In a retrospective cohort study, we identified 387,841 COVID-19 patients through TriNetX.

Temporal Learning Among Prefrontal and Striatal Ensembles.

Behavioral flexibility requires the prefrontal cortex and striatum, but it is unclear if these structures play similar or distinct roles in adapting to novel circumstances. Here, we investigate neuronal ensembles in the medial frontal cortex (MFC) and the dorsomedial striatum (DMS) during one form of behavioral flexibility: learning a new temporal interval. We studied corticostriatal neuronal activity as rodents trained to respond after a 12-s fixed interval (FI12) learned to respond at a shorter 3-s fixed interval (FI3).

Experience-related enhancements in striatal temporal encoding.

Temporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinson's disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement.

Mechanism of Electroacupuncture Regulating IRS-1 Phosphorylation in Skeletal Muscle to Improve Insulin Sensitivity.

Objective: To explore the possible mechanism of electroacupuncture to improve insulin sensitivity in type 2 diabetes rats.

Methods: Fourteen Zucker Diabetic Fatty (ZDF) rats were randomly divided into two groups: a model group and an electroacupuncture group, with 7 rats in each group. Seven Zucker Lean (ZL) rats served as a control group.

Stay or go? Neuronal activity in medial frontal cortex during a voluntary tactile preference task in head-fixed mice.

The decision to move is influenced by sensory, attentional, and motivational cues. One such cue is the quality of the tactile input, with noxious or unpleasant sensations causing an animal to move away from the cue. Processing of painful and unpleasant sensation in the cortex involves multiple brain regions, although the specific role of the brain areas involved in voluntary, rather than reflexive movement away from unpleasant stimuli is not well understood.

Stimulation of Posterior Thalamic Nuclei Induces Photophobic Behavior in Mice.

Objective: A hallmark of migraine is photophobia. In mice, photophobia-like behavior is induced by calcitonin gene-related peptide (CGRP), a neuropeptide known to be a key player in migraine. In this study, we sought to identify sites within the brain from which CGRP could induce photophobia.

Concerted Actions of Octopamine and Dopamine Receptors Drive Olfactory Learning.

Aminergic signaling modulates associative learning and memory. Substantial advance has been made in on the dopamine receptors and circuits mediating olfactory learning; however, our knowledge of other aminergic modulation lags behind. To address this knowledge gap, we investigated the role of octopamine in olfactory conditioning.

Corticostriatal stimulation compensates for medial frontal inactivation during interval timing.

Prefrontal dysfunction is a common feature of brain diseases such as schizophrenia and contributes to deficits in executive functions, including working memory, attention, flexibility, inhibitory control, and timing of behaviors. Currently, few interventions improve prefrontal function. Here, we tested whether stimulating the axons of prefrontal neurons in the striatum could compensate for deficits in temporal processing related to prefrontal dysfunction.

Cerebellar D1DR-expressing neurons modulate the frontal cortex during timing tasks.

Converging lines of evidence suggest that the cerebellum plays an integral role in cognitive function through its interactions with association cortices like the medial frontal cortex (MFC). It is unknown precisely how the cerebellum influences the frontal cortex and what type of information is reciprocally relayed between these two regions. A subset of neurons in the cerebellar dentate nuclei, or the homologous lateral cerebellar nuclei (LCN) in rodents, express D1 dopamine receptors (D1DRs) and may play a role in cognitive processes.

Scopolamine and Medial Frontal Stimulus-Processing during Interval Timing.

Neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and Alzheimer's disease (AD) involve loss of cholinergic neurons in the basal forebrain. Here, we investigate how cholinergic dysfunction impacts the frontal cortex during interval timing, a process that can be impaired in PD and AD patients. Interval timing requires participants to estimate an interval of several seconds by making a motor response, and depends on the medial frontal cortex (MFC), which is richly innervated by basal forebrain cholinergic projections.

Clumping Between Carbon Black and Titanium Dioxide Pigment by Water Vapor Absorption and Its Correlation with Electrophoretic Display.

Carbon black and titanium dioxide have been widely used as pigment particles for electrophoretic displays. However, the effect of external water vapor on these pigment particles has not yet been presented. Therefore, in this work, we report the clumping phenomenon between pigment particles as a result of water vapor absorption.

Prefrontal D1 Dopamine-Receptor Neurons and Delta Resonance in Interval Timing.

Considerable evidence has shown that prefrontal neurons expressing D1-type dopamine receptors (D1DRs) are critical for working memory, flexibility, and timing. This line of work predicts that frontal neurons expressing D1DRs mediate cognitive processing. During timing tasks, one form this cognitive processing might take is time-dependent ramping activity-monotonic changes in firing rate over time.

Dorsal Raphe Serotonin Neurons Mediate CO-Induced Arousal from Sleep.

Arousal from sleep in response to CO is a critical protective phenomenon. Dysregulation of CO-induced arousal contributes to morbidity and mortality from prevalent diseases, such as obstructive sleep apnea and sudden infant death syndrome. Despite the critical nature of this protective reflex, the precise mechanism for CO-induced arousal is unknown.

A human prefrontal-subthalamic circuit for cognitive control.

The subthalamic nucleus is a key site controlling motor function in humans. Deep brain stimulation of the subthalamic nucleus can improve movements in patients with Parkinson's disease; however, for unclear reasons, it can also have cognitive effects. Here, we show that the human subthalamic nucleus is monosynaptically connected with cognitive brain areas such as the prefrontal cortex.

Rodent Medial Frontal Control of Temporal Processing in the Dorsomedial Striatum.

Although frontostriatal circuits are critical for the temporal control of action, how time is encoded in frontostriatal circuits is unknown. We recorded from frontal and striatal neurons while rats engaged in interval timing, an elementary cognitive function that engages both areas. We report four main results.

Projection targets of medial frontal D1DR-expressing neurons.

Prefrontal neurons expressing D1-type dopamine receptors (D1DRs) have been implicated in a variety of cognitive processes including working memory and timing. Although D1DRs are most strongly expressed on layer V/VI projection neurons, it is unknown which brain areas are specifically targeted by these projections. Here we selectively marked D1DR neurons using cre-loxP techniques with AAV carrying mCherry fluorescent protein, and traced projection targets of D1DR+ neurons in the mouse medial frontal cortex (MFC).

Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice.

Disrupted mesocortical dopamine contributes to cognitive symptoms of Parkinson's disease (PD). Past work has implicated medial frontal neurons expressing D1 dopamine receptors (D1DRs) in temporal processing. Here, we investigated whether these neurons can compensate for behavioral deficits resulting from midbrain dopamine dysfunction.

Axial levodopa-induced dyskinesias and neuronal activity in the dorsal striatum.

Levodopa-induced dyskinesias are abnormal involuntary movements that limit the effectiveness of treatments for Parkinson's disease. Although dyskinesias involve the striatum, it is unclear how striatal neurons are involved in dyskinetic movements. Here we record from striatal neurons in mice during levodopa-induced axial dyskinesias.

Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease.

Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity.