Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 8–12% of children globally. Hyperactivity-related behaviors, as well as inattention and impulsivity, are regarded as the nuclear symptoms of ADHD. At present, its etiologies and risk factors are unknown. Previous research linked TARP γ-8 deficiency to ADHD-like behaviors in mice, including hyperactivity, impulsivity, and memory deficits. Aniracetam, a nootropic drug, enhances cognition by modulating cholinergic activity and glutamate receptors, offering neuroprotective effects. This study examined TARP γ-8 knockout (KO) mice at 4 and 8 weeks, assessing behaviors through locomotor activity, cliff avoidance, novel object recognition, and contextual fear conditioning tests. TARP γ-8 KO mice exhibited hyperactivity, reduced recognition memory, and impaired short-term memory and long-term memory. Aniracetam administration improved these behavioral deficits, suggesting its potential as a therapeutic agent for ADHD. The ...

Zebrafish have gained prominence as a model organism in neuroscience over the past several decades, generating key insight into the development and functioning of the vertebrate brain. However, techniques for whole-brain mapping in adult stage zebrafish are lacking. Here, we describe a pipeline built using open-source tools for whole-brain activity mapping in adult zebrafish. Our pipeline combines advances in histology, microscopy, and machine learning to capture c-fos activity across the entirety of the brain. Following tissue clearing, whole-brain images are captured using light-sheet microscopy and registered to the recently created adult zebrafish brain atlas (AZBA) for automated segmentation. By way of example, we used our pipeline to measure brain activity after zebrafish were subject to the novel tank test, one of the most widely used behaviors in adult zebrafish. c-fos levels peaked 15 min following behavior and several regions, including those containing serotoninergic and dopaminergic neurons, we...

Nerve growth factor (NGF) has many effects on sympathetic and sensory neurons, but the mechanisms by which NGF exerts its actions are unknown. We have determined the localization of bound and internalized 125I-NGF by light and electron microscopic radioautography on a cell line derived from a rat pheochromocytoma (PC12). In response to NGF, PC12 cells cease mitosis and develop neuron-like processes. We have localized 125I-NGF (5 ng/ml) in cells without previous exposure to NGF (naive) after a continuous incubation with 125I-NGF for 2 min, 1 hr, 6 hr, 1 day and 1 week, as well as in cells that were grown with NGF (50 ng/ml) for 1 week (primed) and then exposed to 125I-NGF for 15 min, 1 hr, 6 hr, and 1 day. Examination of whole mount radioautographs revealed that all cells were labeled and that the distribution of grains was homogeneous. Primed cells were labeled on neurites and growth cones, as well as on cell bodies, and also had a greater density of labeling than naive cells. These patterns were identical...

Singular strategies for promoting axon regeneration and motor recovery after spinal cord injury (SCI) have been attempted with limited success. For instance, the deletion of RhoA and phosphatase and tensin homolog ( Pten ) (an extrinsic and intrinsic modulating factor, respectively) in corticospinal neurons (CSNs) promotes axon sprouting after thoracic SCI; however, it is unable to restore motor function. Here, we examine the effects of combining RhoA/Pten deletion in CSNs with chemogenetic neuronal stimulation on axonal growth and motor recovery after SCI in mice. We find that this combinatorial approach promotes greater axonal growth and presynaptic bouton formation in CSNs within the spinal cord compared with RhoA ; Pten deletion alone. Furthermore, chemogenetic neuronal stimulation of RhoA ; Pten -deleted CSNs improves forelimb performance in behavioral tasks after SCI compared with RhoA ; Pten deletion alone. These results demonstrate that combination therapies pairing genetic modifications with neuro...

At Neuroscience 2019, 135 abstracts (15 per half-day) will be presented in the dynamic poster format. A dynamic poster is different from a regular poster in that it is displayed on a flat, plasma screen connected to a user-provided electronic device (laptop, tablet, etc.) and allows for multimedia content such as videos, audio clips, and animated images or graphs.

Impulsivity is often considered a risk factor for drug addiction; however, not all evidence supports this view. In the present study, we used a food reward delay-discounting task (DDT) to categorize rats as low-, middle-, and high-impulsive but failed to find any difference among these groups in the acquisition and maintenance of cocaine self-administration (SA), regardless of electrical footshock punishment. Additionally, there were no group differences in locomotor responses to acute cocaine in rats with or without a history of cocaine SA. Unexpectedly, chronic cocaine SA selectively increased impulsive choice in low-impulsive rats. Resting-state fMRI analysis revealed a positive correlation between impulsivity and cerebral blood volume in the midbrain, thalamus, and auditory cortex. Using these three regions as seeds, we observed a negative correlation between impulsivity and functional connectivity between the midbrain and frontal cortex, as well as between the thalamus and frontal cortex (including th...

Humans and nonhumans alike often make choices to gain information, even when the information cannot be used to change the outcome. Prior research has shown that the anterior cingulate cortex (ACC) is important for evaluating options involving reward-predictive information. Here we studied the role of ACC in information choices using optical inhibition to evaluate the contribution of this region during specific epochs of decision-making. Rats could choose between an uninformative option followed by a cue that predicted reward 50% of the time versus a fully informative option that signaled outcomes with certainty but was rewarded only 20% of the time. Reward seeking during the informative S+ cue decreased following ACC inhibition, indicating a causal contribution of this region in supporting reward expectation to a cue signaling reward with certainty. Separately in a positive control experiment and in support of a known role for this region in sustaining high-effort behavior for preferred rewards, we observe...

Orbitofrontal cortex (OFC) damage elicits impulsivity and perseveration, and impairments in OFC function may underlie compulsive drug seeking in cocaine users. To test this hypothesis, we assessed the effects of fiber-sparing lesions or functional inactivation of OFC subregions on cocaine seeking in rats. Rats were trained to lever press for intravenous cocaine (0.20 mg/infusion) paired with the presentations of light plus tone stimuli. Responding was then allowed to extinguish. Rats received bilateral NMDA (0.1 M) or sham lesions of the lateral OFC (lOFC) or medial OFC (mOFC) before self-administration training (experiment 1) or muscimol plus baclofen (0.1 and 1.0 mM) or vehicle infusions into the lOFC or mOFC before reinstatement testing (experiment 2). The effects of these manipulations on reinstatement of cocaine seeking (i.e., responding on the previously cocaine-paired lever) were assessed in the presence of the light plus tone stimuli or after a cocaine priming injection (10 mg/kg, i.p.). Post-train...

We studied the effects of working memory (WM) on semantic neural systems using event-related functional magnetic resonance imaging (fMRI). Semantic congruency was manipulated using a series of visual sentence pairs with predictable endings. In each pair, the first sentence primed contextual expectation for the terminal word in the second sentence. The second sentence ended with either a semantically appropriate or a semantically inappropriate ending. WM was manipulated by increasing the memory set size. Level 1 WM load contained a single prime sentence and Level 2 contained two prime sentences. Task related activation occurred predominately in the left hemisphere and increased as a function of WM load. Interactions between semantic processing and WM effects were examined within the inferior parietal, superior temporal, lateral frontal, and cingulate regions. The correspondence between the current fMRI results and prior work on the manner in which WM influences the semantic N400 response was examined. Overa...

The external globus pallidus (GPe) is a central part of the basal ganglia indirect pathway implicated in movement and decision-making. As a hub connecting the dorsal striatum and subthalamic nucleus (STN), the GPe guides repetitive and routine behaviors. However, it remains unknown how diverse GPe cells engage in routine formation while learning action sequences in repetitive reward-seeking conditioning. Here, in male mice, we investigated the Ca2+ dynamics of two GPe cell types, astrocytes and parvalbumin-expressing neurons, during routine formation. Our findings show that the dynamics of GPe astrocytes may be involved in action sequence refinement, a characteristic potentially contributing to more efficient reward-seeking behavior.