Multiple recent studies have shown that motor activity greatly impacts the activity of primary sensory areas like V1. Yet, the role of this motor related activity in sensory processing is still unclear. Here, we dissect how these behavior signals are broadcast to different layers and areas of the visual cortex. To do so, we leveraged a standardized and spontaneous behavioral fidget event in passively viewing mice. Importantly, this behavior event had no relevance to any ongoing task allowing us to compare its neuronal correlates with visually relevant behaviors (e.g., running). A large two-photon Ca2+ imaging database of neuronal responses uncovered four neural response types during fidgets that were consistent in their proportion and response patterns across all visual areas and layers of the visual cortex. Indeed, the layer and area identity could not be decoded above chance level based only on neuronal recordings. In contrast to running behavior, fidget evoked neural responses that were independent to v...

Accumulating evidence indicates significant consequences for astrocytes associated with drug abuse. For example, reductions in structural features and synaptic colocalization of male rat nucleus accumbens (NAc) astrocytes are observed following short-access (ShA; 2 h/d) self-administration and extinction from cocaine, methamphetamine, and heroin. However, it is unknown whether these observations extend to other rodent models of drug abuse, how enduring these effects may be, and whether similar effects are observed in female rats. Here, we assess the effects of long-access (LgA; 6 h/d) cocaine self-administration and abstinence on NAc astrocytes separately in male and female rats, employing a commonly used behavioral approach to investigate the incubation of cocaine craving. NAc astrocytes from male rats exhibit extensive (∼40%) reductions in surface area, volume, and postsynaptic colocalization 45 d but not 24 h after the last self-administration session. In contrast, no effect of self-administration and a...

Dravet syndrome (DS) is a catastrophic form of pediatric epilepsy mainly caused by noninherited mutations in the SCN1A gene. DS patients suffer severe and life-threatening focal and generalized seizures which are often refractory to available anti-seizure medication. Antisense oligonucleotides (ASOs) based approaches may offer treatment opportunities in DS. MicroRNAs are short noncoding RNAs that play a key role in brain structure and function by post-transcriptionally regulating gene expression, including ion channels. Inhibiting miRNA-134 (miR-134) using an antimiR ASO (Ant-134) has been shown to reduce evoked seizures in juvenile and adult mice and reduce epilepsy development in models of focal epilepsy. The present study investigated the levels of miR-134 and whether Ant-134 could protect against hyperthermia-induced seizures, spontaneous seizures and mortality (SUDEP) in F1. Scn1a( +/− )tm1kea mice. At P17, animals were intracerebroventricular injected with 0.1–1 nmol of Ant-134 and subject to a hyper...

Fragile X syndrome (FXS) is a leading monogenic cause of intellectual disability and autism spectrum disorders, spurring decades of intense research and a multitude of mouse models. So far, these models do not recapitulate the genetic underpinning of classical FXS—CGG repeat-induced methylation of the Fmr1 locus—and their findings have failed to translate into the clinic. We sought to answer whether this disparity was because of low repeat length and generated a novel mouse line with 341 repeats, Fmr1hs341 , which is the largest allele in mice reported to date. This repeat length is significantly longer than the 200 repeats generally required for methylation of the repeat tract and promoter region in FXS patients, which leads to silencing of the FMR1 gene. Bisulfite sequencing fails to detect the robust methylation expected of FXS in Fmr1hs341 mice. Quantitative real-time PCR and Western blotting results also do not resemble FXS and instead produce a biochemical profile consistent with the fragile X-associ...

Neural oscillations are thought to reflect low-level operations that can be used for higher-level cognitive functions. Here, we investigated the role of brain rhythms in the 1–30 Hz range by recording MEG in human participants performing a visual delayed match-to-sample paradigm in which orientation or spatial frequency of sample and probe gratings had to be matched. A cue occurring before or after sample presentation indicated the to-be-matched feature. We demonstrate that alpha/beta power decrease tracks the presentation of the informative cue and indexes faster responses. Moreover, these faster responses coincided with an augmented phase alignment of slow oscillations, as well as phase–amplitude coupling between slow and fast oscillations. Importantly, stimulus decodability was boosted by both low alpha power and high beta power. In summary, we provide support for a comprehensive framework in which different rhythms play specific roles: slow rhythms control input sampling, while alpha (and beta) gates t...

The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Recent experiments showed that recurring cholinergic activation of α7 nACh receptors expressed in oriens-lacunosum-moleculare (OLMα2) interneurons can directly induce LTP in Schaffer collateral (SC)–CA1 synapses. Here, we pair in vitro studies with biophysically based modeling to uncover the underlying mechanisms. According to our model, α7 nAChR activation increases OLM GABAergic activity. This results in the inhibition of the fast-spiking interneurons that provide feedforward inhibition onto CA1 pyramidal neurons. This disinhibition, paired with tightly timed SC stimulation, can induce potentiation at the excitatory synapses of CA1 pyramidal neurons. Our work details the role of cholinergic modulation in disinhibition-induced hippocampal plasticity. It relates the timing of ch...

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 ...

Our brains synthesize vast and varied sensory inputs to represent an event or place that can later be recalled freely. The term “engram” refers to a group of neurons activated in association with a memory or event, suggesting that if one were to activate a subset of cells in the ensemble, one would trigger the recall of a memory. The medial temporal lobes, including the hippocampus, are often studied as the primary region of spatial engram formation (Josselyn and Tonegawa, 2020). However, newly formed spatial memory representations are incredibly transient. Following encoding, consolidation from the hippocampus to related cortical structures is critical for stable memory retention (Wirt and Hyman, 2017). What happens when this process of generating stable long-term memories is disrupted? Neuronal hyperactivity, seen in seizures, potentially corrupts existing engrams and is often associated with retrograde amnesia in humans. Retrograde amnesia, or forgetting recently formed memories, could be because of dis...

The ability to detect faces in the environment is of utmost ecological importance for human social adaptation. While face categorization is efficient, fast and robust to sensory degradation, it is massively impaired when the facial stimulus does not match the natural contrast statistics of this visual category, i.e., the typically experienced ordered alternation of relatively darker and lighter regions of the face. To clarify this phenomenon, we characterized the contribution of natural contrast statistics to face categorization. Specifically, 31 human adults viewed various natural images of nonface categories at a rate of 12 Hz, with highly variable images of faces occurring every eight stimuli (1.5 Hz). As in previous studies, neural responses at 1.5 Hz as measured with high-density electroencephalography (EEG) provided an objective neural index of face categorization. Here, when face images were shown in their naturally experienced contrast statistics, the 1.5-Hz face categorization response emerged ove...

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 peripherals, 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-...