Traditional human electroencephalography experiments that study visuomotor processing use controlled laboratory conditions with limited ecological validity. In the real world, the brain integrates complex, dynamic, multimodal visuomotor cues to guide the execution of movement. The parietal and occipital cortices are especially important in the online control of goal-directed actions. Table tennis is a whole-body, responsive activity requiring rapid visuomotor integration that presents a myriad of unanswered neurocognitive questions about brain function during real world movement. The aim of this study was to quantify the electrocortical dynamics of the parieto-occipital cortices while playing a sport with high-density electroencephalography. We included analysis of power spectral densities, event-related spectral perturbations, intertrial phase coherences, event-related potentials, and event-related phase coherences of parieto-occipital source-localized clusters while participants played table tennis with ...

Intracortical microstimulation (ICMS) is commonly used in many experimental and clinical paradigms; however, its effects on the activation of neurons are still not completely understood. To document the responses of cortical neurons in awake non-human primates to stimulation, we recorded single-unit activity while delivering single-pulse stimulation via Utah arrays implanted in primary motor cortex of three macaque monkeys. Stimuli between 5-50 μA delivered to single channels reliably evoked spikes in neurons recorded throughout the array with delays of up to 12 milliseconds. ICMS pulses also induced a period of inhibition lasting up to 150 ms that typically followed the initial excitatory response. Higher current amplitudes led to a greater probability of evoking a spike and extended the duration of inhibition. The likelihood of evoking a spike in a neuron was dependent on the spontaneous firing rate as well as the delay between its most recent spike time and stimulus onset. Tonic repetitive stimulation b...

In addition to brain disorders, which constitute a devastating consequence of prenatal alcohol exposure (PAE), eye development is also significantly affected. Given that the retina is a readily accessible part of the central nervous system, a better understanding of the impact of ethanol on retinal development might provide ophthalmological landmarks helpful for early diagnosis of foetal alcohol syndrome. This study aimed to provide a fine morphometric and cellular characterization of the development of retinal microvasculature and neurovascular interactions in a mouse model of foetal alcohol spectrum disorder. The data revealed that PAE impaired superficial vascular plexus development. In particular, progression of the vascular migration front was significantly decreased in PAE retinas, supporting a delay in plexus progression. Moreover, a significant decrease in the vessel density and number of perforating vessels was quantified in PAE mice, supporting less angiogenesis. The present study provides also t...

A rapidly approaching dark object evokes an evolutionarily conserved fear response in both vertebrates and invertebrates, young to old. A looming visual stimulus mimics an approaching object and triggers a similarly robust fear response in mice, resulting in freeze and flight. However, the retinal neural pathway responsible for this innate response has not been fully understood. We first explored a variety of visual stimuli that reliably induced these innate responses, and found that a looming stimulus with two-day acclimation consistently evoked fear responses. Because the fear responses were triggered by the looming stimulus with moving edges, but not by a screen flipping from light to dark, we targeted the starburst amacrine cells (SACs), crucial neurons for retinal motion detection. We utilized intraocular injection of diphtheria toxin (DT) in mutant mice expressing diphtheria toxin receptors (DTR) in SACs. The looming-evoked fear responses disappeared in half of the DT-injected mice, and the other mic...

Loss-of-function mutations in Reelin and DAB1 signaling pathways disrupt proper neuronal positioning in the cerebral neocortex and hippocampus, but the underlying molecular mechanisms remain elusive. Here, we report that heterozygous yotari mice harboring a single autosomal recessive yotari mutation of Dab1 exhibited a thinner neocortical layer 1 than wild-type mice on postnatal day (P)7. However, a birth-dating study suggested that this reduction was not caused by failure of neuronal migration. In utero electroporation-mediated sparse labeling revealed that the superficial layer neurons of heterozygous yotari mice tended to elongate their apical dendrites within layer 2 than within layer 1. In addition, the CA1 pyramidal cell layer in the caudo-dorsal hippocampus was abnormally split in heterozygous yotari mice, and a birth-dating study revealed that this splitting was caused mainly by migration failure of late-born pyramidal neurons. Adeno-associated virus (AAV)-mediated sparse labeling further showed th...

Anxiety is one of the most common psychiatric disorders diagnosed in the United States today. Like all mental illnesses, anxiety pathology includes genetic, molecular, somatic, and behavioral characteristics. Specific brain regions implicated in anxiety include the prefrontal cortex, amygdala, hippocampus, and hypothalamus. Together, these regions regulate fear-related learning and memory processes, and are innervated by neuronal projections that use glutamate and GABA as neurotransmitters. Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) are also implicated in anxiety. This review discusses the neuroepigenetics of the anxiety phenotype. While studying such changes is limited to postmortem brain studies or peripheral tissue acquisition in humans, the use of animals to model anxiety phenotypes has made epigenetic research possible. In this review, we summarize and discuss a plethora of DNA methylation, histone modification, and associated gene expression differences underscoring the anx...

Previous investigation of cognitive processes using transcranial magnetic stimulation (TMS) have explored the response to different stimulation parameters such as frequency and coil location. In this study, we attempt to add another parameter by exploiting the spatial profiles of TMS coils to infer regional information concerning reward-related behavior. We used different TMS coils to modulate activity in the prefrontal cortex (PFC) and examined resulting changes in behavior and associated brain activity. More specifically, we used the Figure-8 coil to stimulate a portion of the dorsolateral PFC (DLPFC) and the H-Coil to stimulate a larger volume within the lateral PFC (LPFC). Healthy human volunteers completed behavioral questionnaires ( n  = 29) or performed a reward-related decision-making functional MRI (fMRI) task ( n  = 21) immediately before and after acute high-frequency stimulation (10 Hz) with either a Figure-8 coil, H-Coil, or a sham coil. Stimulation was found to induce behavioral changes as we...

Loss-of-function mutations in neuroligin-4 (Nlgn4), a member of the neuroligin family of postsynaptic adhesion proteins, cause autism spectrum disorder in humans. Nlgn4 knockout (KO) in mice leads to social behavior deficits and complex alterations of synaptic inhibition or excitation, depending on the brain region. In the present work, we comprehensively analyzed synaptic function and plasticity at the cellular and network levels in hippocampal dentate gyrus of Nlgn4 KO mice. Compared with wild-type littermates, adult Nlgn4 KO mice exhibited increased paired-pulse inhibition of dentate granule cell population spikes, but no impairments in excitatory synaptic transmission or short-term and long-term plasticity in vivo . In vitro patch-clamp recordings in neonatal organotypic entorhino-hippocampal slice cultures from Nlgn4 KO and wild-type littermates revealed no significant differences in excitatory or inhibitory synaptic transmission, homeostatic synaptic plasticity, and passive electrotonic properties in...

When deciding while acting, such as sequentially selecting targets during naturalistic foraging, movement trajectories reveal the dynamics of the unfolding decision process. Ongoing and planned actions may impact decisions in these situations in addition to expected reward outcomes. Here, we test how strongly humans weigh and how fast they integrate individual constituents of expected value, namely the prior probability (PROB) of an action and the prior expected reward amount (AMNT) associated with an action, when deciding based on the combination of both together during an ongoing movement. Unlike other decision-making studies, we focus on PROB and AMNT priors, and not final evidence, in that correct actions were either instructed or could be chosen freely. This means, there was no decision-making under risk. We show that both priors gradually influence movement trajectories already before mid-movement instructions of the correct target and bias free-choice behavior. These effects were consistently strong...

Brain stores new information by modifying connections between neurons. When new information is learnt, a group of neurons gets activated and they are connected to each other via synapses. Dendritic spines are protrusions along neuronal dendrites where excitatory synapses are located. Dendritic spines are the first structures to protrude out from the dendrite to reach out to other neurons and establish a new connection. Thus, it is expected that neuronal activity enhances spine initiation. However, the molecular mechanisms linking neuronal activity to spine initiation are poorly known. Membrane binding BAR domain proteins are involved in spine initiation, but it is not known whether neuronal activity affects BAR domain proteins. Here, we used bicuculline treatment to activate excitatory neurons in organotypic hippocampal slices. With this experimental setup, we identified F-BAR domain containing growth arrest-specific protein (Gas7) as a novel spine initiation factor responding to neuron activity. Upon bicu...