Migraine is believed to be initiated by neuronal activity in the CNS that triggers excitation of nociceptive trigeminal ganglion (TG) nerve fibers innervating the meninges and thus causes a unilateral throbbing headache. Drugs that precipitate or potentiate migraine are known to elevate intracellular levels of the cyclic nucleotides cAMP or cGMP, while anti-migraine treatments couple to signaling pathways that reduce cAMP or cGMP, suggesting an involvement of these cyclic nucleotides in migraine. Members of the HCN ion channel family are activated by direct binding of cAMP or cGMP, suggesting in turn that a member of this family may be a critical trigger of migraine. Here, we show that pharmacological block or targeted genetic deletion of HCN2 abolished migraine-like pain in three rodent migraine models (in both sexes). Induction of migraine-like pain in these models triggered expression of the protein C-FOS, a marker of neuronal activity, in neurons of the trigeminocervical complex (TCC), where TG neurons...

Reaction time is accelerated if a loud (startling) sound accompanies the cue—the “StartReact” effect. Animal studies revealed a reticulospinal substrate for the startle reflex; StartReact may similarly involve the reticulospinal tract, but this is currently uncertain. Here we trained two female macaque monkeys to perform elbow flexion/extension movements following a visual cue. The cue was sometimes accompanied by a loud sound, generating a StartReact effect in electromyogram response latency, as seen in humans. Extracellular recordings were made from antidromically identified corticospinal neurons in primary motor cortex (M1), from the reticular formation (RF), and from the spinal cord (SC; C5–C8 segments). After loud sound, task-related activity was suppressed in M1 (latency, 70–200 ms after cue), but was initially enhanced (70–80 ms) and then suppressed (140–210 ms) in RF. SC activity was unchanged. In a computational model, we simulated a motoneuron pool receiving input from different proportions of th...

Pregnancy is associated with extraordinary plasticity in the maternal brain. Studies in humans and other mammals suggest extensive structural and functional remodeling of the female brain during and after pregnancy. However, we understand remarkably little about the molecular underpinnings of this natural phenomenon. To gain insight into pregnancy-associated hippocampal plasticity, we performed single nucleus RNA-seq and single nucleus ATAC-seq from the mouse hippocampus before, during, and after pregnancy. We identified cell-type-specific transcriptional and epigenetic signatures associated with pregnancy and post-partum adaptation. In addition, we analyzed receptor-ligand interactions and transcription factor motifs that inform hippocampal cell type identity and provide evidence of pregnancy-associated adaption. In total, this data provides a unique resource of coupled transcriptional and epigenetic data across a dynamic time period in the mouse hippocampus and suggests opportunities for functional inter...

Video recording is essential for behavioral neuroscience research, but the majority of available systems suffer from poor cost-to-functionality ratio. Commercial options frequently come at high financial cost that prohibits scalability and throughput, whereas DIY solutions often require significant expertise and time investment unaffordable to many researchers. To address this, we combined a low-cost Raspberry Pi microcomputer, DIY electronics peripheries, freely available open-source firmware, and custom 3D printed casings to create Pi USB Cam, a simple yet powerful and highly versatile video recording solution. Pi USB Cam is constructed using affordable and widely available components and requires no expertise to build and implement. The result is a system that functions as a plug-and-play USB camera that can be easily installed in various animal testing and housing sites and is readily compatible with popular behavioral and neural recording software. Here, we provide a comprehensive parts list and step-...

fMRI studies that investigate somatotopic tactile representations in the human cortex typically use either block or phase-encoded stimulation designs. Event-related (ER) designs allow for more flexible and unpredictable stimulation sequences than the other methods, but they are less efficient. Here, we compared an efficiency-optimized fast ER design (2.8-s average intertrial interval; ITI) to a conventional slow ER design (8-s average ITI) for mapping voxelwise fingertip tactile tuning properties in the sensorimotor cortex of six participants at 7 Tesla. The fast ER design yielded more reliable responses compared with the slow ER design, but with otherwise similar tuning properties. Concatenating the fast and slow ER data, we demonstrate in each individual brain the existence of two separate somatotopically-organized tactile representations of the fingertips, one in the primary somatosensory cortex (S1) on the postcentral gyrus, and the other shared across the motor and premotor cortices on the precentral ...

The subthalamic nucleus (STN) is a small, excitatory nucleus that regulates the output of basal ganglia motor circuits. The functions of the STN and its role in the pathophysiology of Parkinson’s disease are now well established. However, some basic characteristics like the developmental origin and molecular phenotype of neuronal subpopulations are still being debated. The classical model of forebrain development attributed the origin of STN within the diencephalon. Recent studies of gene expression patterns exposed shortcomings of the classical model. To accommodate these findings, the prosomeric model was developed. In this concept, STN develops within the hypothalamic primordium, which is no longer a part of the diencephalic primordium. This concept is further supported by the expression patterns of many transcription factors. It is interesting to note that many transcription factors involved in the development of the STN are also involved in the pathogenesis of neurodevelopmental disorders. Thus, the s...

In times of stress or danger, the autonomic nervous system (ANS) signals the fight or flight response. A canonical function of ANS activity is to globally mobilize metabolic resources, preparing the organism to respond to threat. Yet a body of research has demonstrated that, rather than displaying a homogenous pattern across the body, autonomic responses to arousing events, as measured through changes in electrodermal activity (EDA), can differ between right and left body locations. Surprisingly, an attempt to identify a function of ANS asymmetry consistent with its metabolic role has not been investigated. In the current study, we investigated whether asymmetric autonomic responses could be induced through limb-specific aversive stimulation. Participants were given mild electric stimulation to either the left or right arm while EDA was monitored bilaterally. In a group-level analyses, an ipsilateral EDA response bias was observed, with increased EDA response in the hand adjacent to the stimulation. This e...

There is currently no robust method to evaluate how built environment design affects our emotion. Understanding emotion is significant, as it influences cognitive processes, behavior, and wellbeing, and is linked to the functioning of physiological systems. As mental health problems are becoming more prevalent, and exposure to indoor environments is increasing, it is important we develop rigorous methods to understand whether design elements in our environment affect emotion. This study examines whether the scale of interior built environments modulate neural networks involved in emotion regulation. Using a Cave Automatic Virtual Environment (CAVE) and controlling for indoor environmental quality (IEQ), 66 adults (31 female, aged 18–55) were exposed to context-neutral enclosed indoor room scenes to understand whether built environment scale affected self-report, autonomic nervous system, and central nervous system correlates of emotion. Our results revealed enlarged scale increased electroencephalography (...

Children exposed prenatally to opioids are at an increased risk for behavioral problems and executive function deficits. The prefrontal cortex (PFC) and amygdala (AMG) regulate executive function and social behavior and are sensitive to opioids prenatally. Opioids can bind to toll-like receptor 4 (TLR4) to activate microglia, which may be developmentally important for synaptic pruning. Therefore, we tested the effects of perinatal morphine exposure on executive function and social behavior in male and female mouse offspring, along with microglial-related and synaptic-related outcomes. Dams were injected once daily subcutaneously with saline ( n  = 8) or morphine (MO; 10 mg/kg; n  = 12) throughout pregestation, gestation, and lactation until offspring were weaned on postnatal day 21 (P21). Male MO offspring had impairments in attention and accuracy in the five-choice serial reaction time task, while female MO offspring were less affected. Targeted gene expression analysis at P21 in the PFC identified altera...

Psychology and neuroscience research have shown that fractioning operations among several individuals along a hierarchical chain allows diffusing responsibility between components of the chain, which has the potential to disinhibit antisocial actions. Here, we present two studies, one using fMRI (Study 1) and one using EEG (Study 2), designed to help understand how commanding or being in an intermediary position impacts the sense of agency and empathy for pain. In the age of military drones, we also explored whether commanding a human or robot agent influences these measures. This was done within a single behavioral paradigm in which participants could freely decide whether or not to send painful shocks to another participant in exchange for money. In Study 1, fMRI reveals that activation in social cognition-related and empathy-related brain regions was equally low when witnessing a victim receive a painful shock while participants were either commander or simple intermediary transmitting an order, compare...