In implicit sensorimotor adaptation, a mismatch between the predicted and actual sensory feedback results in a sensory prediction error (SPE). Sensory predictions have long been thought to be linked to descending motor commands, implying a necessary contribution of movement execution to adaptation. However, recent work has shown that mere motor imagery (MI) also engages predictive mechanisms, opening up the possibility that MI might be sufficient to drive implicit adaptation. In a within-subject design in humans ( n  = 30), implicit adaptation was assessed in a center-out reaching task, following a single exposure to a visuomotor rotation. It was hypothesized that performing MI of a reaching movement while being provided with an animation of rotated visual feedback (MI condition) would lead to postrotation biases (PRBs) similar to those observed when the movement is executed (Execution condition). Results revealed that both the MI and Execution conditions led to significant directional biases following rot...

Estradiol, a female sex hormone and the predominant form of estrogen, has diverse effects throughout the brain including in learning and memory. Estradiol modulates several types of learning that depend on the dorsomedial striatum (DMS), a subregion of the basal ganglia involved in goal-directed learning, cued action-selection, and motor skills. A cellular basis of learning is synaptic plasticity, and the presence of extranuclear estradiol receptors ERα, ERβ, and G-protein-coupled estrogen receptor (GPER) throughout the DMS suggests that estradiol may influence rapid cellular actions including those involved in plasticity. To test whether estradiol affects synaptic plasticity in the DMS, corticostriatal long-term potentiation (LTP) was induced using theta-burst stimulation (TBS) in ex vivo brain slices from intact male and female C57BL/6 mice. Extracellular field recordings showed that female mice in the diestrous stage of the estrous cycle exhibited LTP similar to male mice, while female mice in estrus di...

Several neurodevelopmental disorders are associated with increased mTOR activity that results in pathogenic neuronal dysmorphogenesis (i.e., soma and dendrite overgrowth), leading to circuit alterations associated with epilepsy and neurologic disabilities. Although an mTOR analog is approved for the treatment of epilepsy in one of these disorders, it has limited efficacy and is associated with a wide range of side effects. There is a need to develop novel agents for the treatment of mTOR-pathway related disorders. Here, we developed a medium-throughput phenotypic assay to test drug efficacy on neurite morphogenesis of mouse neurons in a hyperactive mTOR condition. Our assay involved in utero electroporation (IUE) of a selective population of cortical pyramidal neurons with a plasmid encoding the constitutively active mTOR activator, Rheb, and tdTomato. Labeled neurons from the somatosensory cortex (SSC) were cultured onto 96-well plates and fixed at various days in vitro or following Torin 1 treatment. Aut...

Local field potential (LFP) recording is a valuable method for assessing brain systems communication. Multiple methods have been developed to collect LFP data to study the rhythmic activity of the brain. These methods range from the use of single or bundled metal electrodes to electrode arrays that can target multiple brain regions. Although these electrodes are efficient in collecting LFP activity, they can be expensive, difficult to build, and less adaptable to different applications, which may include targeting multiple brain regions simultaneously. Here, the building process for a 16-channel customizable multielectrode array (CMEA) that can be used to collect LFP data from different brain regions simultaneously in rats is described. These CMEA electrode arrays are lightweight (<1 g), take little time to build (<1 h), and are affordable ($15 Canadian). The CMEA can also be modified to record single-unit and multiunit activity in addition to LFP activity using both wired and wireless neural data acquisit...

One of the most prevalent deficits in autism spectrum disorder (ASD) are sensitivities to sensory stimuli. Despite the prevalence of sensory deficits in autism, there are few paradigms capable of easily assessing sensory behaviors in ASD-like mouse models. We addressed this need by creating the Somatosensory Nose-poke Adapted Paradigm (SNAP), which consists of an elevated platform with 6 holes in the center, half of which are lined with sandpaper and half are smooth, requiring mice to use their whiskers to sense the texture. The SNAP paradigm assesses tactile sensory preferences as well as stereotypy, anxiety, and locomotion. We used two wild-type (neurotypical) mouse strains, C57BL/6J (C57) inbred and CD-1 outbred mice, and two ASD mouse models, BTBR (a model of idiopathic ASD) and Cntnap2 −/− mice (a model of syndromic ASD). We found that both ASD models produced more nose pokes into the rough condition than the smooth condition, suggesting an increased preference for complex tactile stimulation when com...

Discerning the contribution of specific ionic currents to complex neuronal dynamics is a difficult, but important, task. This challenge is exacerbated in the human setting, although the widely characterized uniqueness of the human brain compared with preclinical models necessitates the direct study of human neurons. Neuronal spiking frequency preference is of particular interest given its role in rhythm generation and signal transmission in cortical circuits. Here, we combine the frequency-dependent gain (FDG), a measure of spiking frequency preference, and novel in silico analyses to dissect the contributions of individual ionic currents to the suprathreshold features of human layer 5 (L5) neurons captured by the FDG. We confirm that a contemporary model of such a neuron, primarily constrained to capture subthreshold activity driven by the hyperpolarization-activated cyclic nucleotide gated (h-) current, replicates key features of the in vitro FDG both with and without h-current activity. With the model c...

Traumatic brain injury (TBI) elicits neuronal loss at the site of injury and progressive neuronal loss in the penumbra. However, the consequences of TBI on afferent neurons projecting to the injured tissue from distal locations is unknown. Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple brain regions including the cortex, regulate many cognitive functions, and are compromised in numerous neurodegenerative disorders. To determine the consequence of cortical injury on these afferent neurons, we used the fluid percussion injury model of traumatic brain injury and assessed the effects on BFCN survival and axon integrity in male and female mice. Survival or death of BF neurons can be regulated by neurotrophins or proneurotrophins, respectively. The injury elicited an induction of proNGF and proBDNF in the cortex and a loss of BFCNs ipsilateral to the injury compared with sham uninjured mice. The p75NTR knock-out mice did not show loss of BFCN neurons, indicating a retrograde dege...

Volatile anesthetics reduce excitatory synaptic transmission by both presynaptic and postsynaptic mechanisms which include inhibition of depolarization-evoked increases in presynaptic Ca2+ concentration and blockade of postsynaptic excitatory glutamate receptors. The presynaptic sites of action leading to reduced electrically evoked increases in presynaptic Ca2+ concentration and Ca2+-dependent exocytosis are unknown. Endoplasmic reticulum (ER) of Ca2+ release via ryanodine receptor 1 (RyR1) and uptake by SERCA are essential for regulation intracellular Ca2+ and are potential targets for anesthetic action. Mutations in sarcoplasmic reticulum (SR) release channels mediate volatile anesthetic-induced malignant hyperthermia (MH), a potentially fatal pharmacogenetic condition characterized by unregulated Ca2+ release and muscle hypermetabolism. However, the impact of MH mutations on neuronal function are unknown. We used primary cultures of postnatal hippocampal neurons to analyze volatile anesthetic-induced c...

We investigated morphologic changes in the corticospinal tract (CST) to understand the mechanism underlying recovery of hand function after lesion of the CST at the C4/C5 border in seven macaque monkeys. All monkeys exhibited prominent recovery of precision grip success ratio within a few months. The trajectories and terminals of CST from the contralesional ( n  = 4) and ipsilesional ( n  = 3) hand area of primary motor cortex (M1) were investigated at 5–29 months after the injury using an anterograde neural tracer, biotinylated dextran amine (BDA). Reorganization of the CST was assessed by counting the number of BDA-labeled axons and bouton-like swellings in the gray and white matters. Rostral to the lesion (at C3), the number of axon collaterals of the descending axons from both contralesional and ipsilesional M1 entering the ipsilesional and contralesional gray matter, respectively, were increased. Caudal to the lesion (at C8), axons originating from the contralesional M1, descending in the preserved gr...

Simultaneous adaptation to opposite visuomotor perturbations is known to be difficult. It has been shown to be possible only in situations where the two tasks are associated with different contexts, being either a different colored background, a different area of workspace, or a different follow-through movement. However, many of these elements evoke explicit mechanisms that could contribute to storing separate (modular) memories. It remains to be shown whether simultaneous adaptation to multiple perturbations is possible when they are introduced in a fully implicit manner. Here, we sought to test this possibility using a visuomotor perturbation small enough to eliminate explicit awareness. Participants ( N  = 25) performed center-out reaching movements with a joystick to five targets located 72° apart. Depending on the target, visual feedback of cursor position was either veridical (one target) or could be rotated by +5 or −5° (two targets each). After 300 trials of adaptation (60 to each target), results...