The role of striatum in controlling waiting during reactive and self-timed behaviors The ability to wait before responding is crucial for many cognitive functions, including reaction time tasks, where one must resist premature actions before the stimulus and respond quickly once the stimulus is presented. However, the brain regions governing waiting remain unclear. Using localized excitotoxic lesions, we investigated the roles of the motor cortex (MO) and sensorimotor dorsolateral striatum (DLS) in male rats performing a conditioned lever release task with variable delays. Neural activity in both MO and DLS showed similar firing patterns during waiting and responding periods. However, only bilateral DLS lesions caused a sustained increase in premature (anticipatory) responses, whereas bilateral MO lesions primarily prolonged reaction times. In a self-timing version of the task, where rats held a lever for a fixed delay before release, DLS lesions caused a leftward shift in response timing, leading to persistently greater premature responses. These waiting deficits were accompanied by reduced motor vigor, such as slower reward-orienting locomotion. Our findings underscore the critical role of the sensorimotor striatum in regulating waiting behavior in timing-related behaviors.
Suspension as a mood Suspension of judgment is a ubiquitous phenomenon in our lives. It is also relevant for several debates in contemporary epistemology (e.g., evidentialism/pragmatism; peer-disagreement/higher-order evidence; inquiry). The goal of this paper is to arrive at a better understanding of what suspension of judgment is. We first question the popular assumption that we call the Triad view according to which there are three and only three (paradigmatic) doxastic attitudes, namely, belief, disbelief, and suspension of judgment. We elaborate a cumulative argument regarding crucial differences between belief/disbelief and suspension and conclude tentatively that suspension is not a doxastic state. On the constructive side, we defend the positive thesis (with special attention to justification/rationality and reasons for suspension) that suspension is rather an affective phenomenon, viz. a sort of mood. Finally, we consider further consequences of our view for contemporary debates in epistemology, and how it relates to ancient skepticism.
Effects of impulsivity and emotions on time perception: Laboratory behavioral measures Impulsivity is consistently linked to various problematic behaviors, including aggression, substance abuse, pathological gambling, risky driving, and numerous psychopathological disorders such as attention deficit hyperactivity disorder and personality disorders. This study aims to investigate the relationship between self-reported impulsivity, measured by the Behavioral Inhibition/Behavioral Activation Scales, and emotional states (pleasant, unpleasant, or neutral), in the context of time estimation deviations. A time estimation task was administered to 129 adult participants (88 females) from the community to assess this deviation. The findings reveal that participants underestimated time across all emotional conditions, enhancing our understanding of how impulsivity relates to time perception. Therefore, it is crucial to continue neuropsychophysiological research on impulsivity to explore its causes, manifestations, and connections with other aspects of cognitive and affective functioning. This research will lead to a more precise definition and comprehensive understanding of impulsive behavior.
Born to count: a biological basis of mathematics As languages, mathematics is a biological product and thus based on causal processes of two time scales, namely neural mechanisms and evolution. In this commentary, I will try to figure out possible scenarios responsible for the chick mathematics raised by the target article, focusing on discreteness and transposability of natural numbers.
A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics For accurate perception and motor control, an animal must distinguish between sensory experiences elicited by external stimuli and those elicited by its own actions. The diversity of behaviors and their complex influences on the senses make this distinction challenging. Here, we uncover an action–cue hub that coordinates motor commands with visual processing in the brain’s first visual relay. We show that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge center, integrating visual translational optic flow signals with motor copies from saccades, locomotion and pupil dynamics. The vLGN relays these signals to correct action-specific visual distortions and to refine perception, as shown for the superior colliculus and in a depth-estimation task. Simultaneously, brain-wide vLGN projections drive corrective actions necessary for accurate visuomotor control. Our results reveal an extended corollary discharge architecture that refines early visual transformations and coordinates actions via a distributed hub-and-spoke network to enable visual perception during action.
The dynamic axon initial segment: From neuronal polarity to network homeostasis The axon initial segment (AIS) is a highly specialized compartment in neurons that resides in between axonal and somatodendritic domains. The localization of the AIS in the proximal part of the axon is essential for its two major functions: generating and modulating action potentials and maintaining neuron polarity. Recent findings revealed that the incredibly stable AIS is generated from highly dynamic components and can undergo extensive structural and functional changes in response to alterations in activity levels. These activity-dependent alterations of AIS structure and function have profound consequences for neuronal functioning, and AIS plasticity has emerged as a key regulator of network homeostasis. This review highlights the functions of the AIS, its architecture, and how its organization and remodeling are influenced by developmental plasticity and both acute and chronic adaptations. It also discusses the mechanisms underlying these processes and explores how dysregulated AIS plasticity may contribute to brain disorders.
Contribution of Glutamatergic and GABAergic Mechanisms to the Plasticity-Modulating Effects of Dopamine in the Human Motor Cortex Dopamine, a key neuromodulator in the central nervous system, regulates cortical excitability and plasticity by interacting with glutamate and GABA receptors, which are affected by dopamine receptor subtypes (D1- and D2-like). Non-invasive brain stimulation techniques can induce plasticity and monitor cortical facilitation and inhibition in humans. In a randomized, placebo-controlled, double-blinded study, we investigated how dopamine and D1- and D2-like receptors impact transcranial direct current stimulation (tDCS)-induced plasticity concerning glutamatergic and GABAergic mechanisms. Eighteen healthy volunteers received 1 mA anodal (13 min) and cathodal tDCS (9 min) over the left motor cortex combined with the dopaminergic agents l-dopa (general dopamine activation), bromocriptine (D2-like receptor agonist), combined D2 antagonism via sulpiride and general dopaminergic activation via l-dopa to activate D1-like receptors, and placebo medication. Glutamate-related cortical facilitation and GABA-related cortical inhibition were monitored using transcranial magnetic stimulation techniques, including I–O curve, intracortical facilitation (ICF), short-interval intracortical inhibition (SICI), and I-wave facilitation protocols. Our results indicate that anodal tDCS alone enhanced the I–O curve and ICF while decreasing SICI. Conversely, cathodal tDCS decreased the I-O curve and ICF while increasing SICI. General dopamine and D2 receptor activation combined with anodal tDCS decreased the I-O curve and ICF, but enhanced SICI compared to tDCS alone. When paired with cathodal tDCS, general Dopamine and D2-like receptor activity enhancement prolonged the cathodal tDCS effect on excitability. After anodal tDCS, D1-like receptor activation increased the I-O curve and ICF while reducing SICI. These effects were abolished with cathodal tDCS. Dopaminergic substances combined with anodal and cathodal tDCS did not have a significant effect on I-wave facilitation. These results suggest that D1-like receptor activation enhanced LTP-like plasticity and abolished LTD-like plasticity via glutamatergic NMDA receptor enhancement, while global dopaminergic and D2-like receptor enhancement weakened LTP-like but strengthened LTD-like plasticity primarily via glutamatergic NMDA receptor activity diminution.
Impairment of DET1 causes neurological defects and lethality in mice and humans COP1 and DET1 are components of an E3 ubiquitin ligase that is conserved from plants to humans. Mammalian COP1 binds to DET1 and is a substrate adaptor for the CUL4A-DDB1-RBX1 RING E3 ligase. Transcription factor substrates, including c-Jun, ETV4, and ETV5, are targeted for proteasomal degradation to effect rapid transcriptional changes in response to cues such as growth factor deprivation. Here, we link a homozygous DET1R26W mutation to lethal developmental abnormalities in humans. Experimental cryo-electron microscopy of the DET1 complex with DDB1 and DDA1, as well as co-immunoprecipitation experiments, revealed that DET1R26W impairs binding to DDB1, thereby compromising E3 ligase function. Accordingly, human-induced pluripotent stem cells homozygous for DET1R26W expressed ETV4 and ETV5 highly, and exhibited defective mitochondrial homeostasis and aberrant caspase-dependent cell death when differentiated into neurons. Neuronal cell death was increased further in the presence of Det1-deficient microglia as compared to WT microglia, indicating that the deleterious effects of the DET1 p.R26W mutation may stem from the dysregulation of multiple cell types. Mice lacking Det1 died during embryogenesis, while Det1 deletion just in neural stem cells elicited hydrocephalus, cerebellar dysplasia, and neonatal lethality. Our findings highlight an important role for DET1 in the neurological development of mice and humans.