Visual representations can be generated via feedforward or feedback processes. The extent to which these processes result in overlapping representations remains unclear. Previous work has shown that imagined stimuli elicit similar representations as perceived stimuli throughout the visual cortex. However, while representations during imagery are indeed only caused by feedback processing, neural processing during perception is an interplay of both feedforward and feedback processing. This means that any representational overlap could be because of overlap in feedback processes. In the current study, we aimed to investigate this issue by characterizing the overlap between feedforward- and feedback-initiated category representations during imagined stimuli, conscious perception, and unconscious processing using fMRI in humans of either sex. While all three conditions elicited stimulus representations in left lateral occipital cortex (LOC), significant similarities were observed only between imagery and consci...

Atypical sensory processing is currently included within the diagnostic criteria of autism. The cerebellum is known to integrate sensory inputs of different modalities through its connectivity to the cerebral cortex. Interestingly, cerebellar malformations are among the most replicated features found in postmortem brain of individuals with autism. We studied sensory processing in the cerebellum in a mouse model of autism, knock-out (KO) for the Cntnap2 gene. Cntnap2 is widely expressed in Purkinje cells (PCs) and has been recently reported to regulate their morphology. Further, individuals with CNTNAP2 mutations display cerebellar malformations and CNTNAP2 antibodies are associated with a mild form of cerebellar ataxia. Previous studies in the Cntnap2 mouse model show an altered cerebellar sensory learning. However, a physiological analysis of cerebellar function has not been performed yet. We studied sensory evoked potentials in cerebellar Crus I/II region on electrical stimulation of the whisker pad in a...

Epilepsy affects 3.4 million people in the United States, and, despite the availability of numerous antiepileptic drugs, 36% of patients have uncontrollable seizures, which severely impact quality of life. High-frequency oscillations (HFOs) are a potential biomarker of epileptogenic tissue that could be useful in surgical planning. As a result, research into the efficacy of HFOs as a clinical tool has increased over the last 2 decades. However, detection and identification of these transient rhythms in intracranial electroencephalographic recordings remain time-consuming and challenging. Although automated detection algorithms have been developed, their results are widely inconsistent, reducing reliability. Thus, manual marking of HFOs remains the gold standard, and manual review of automated results is required. However, manual marking and review are time consuming and can still produce variable results because of their subjective nature and the limitations in functionality of existing open-source softwar...

Relapse is a major challenge to the treatment of substance use disorders. A progressive increase in cue-induced drug craving, termed incubation of craving, is observed after withdrawal from multiple drugs of abuse in humans and rodents. Incubation of cocaine craving involves the strengthening of excitatory synapses onto nucleus accumbens (NAc) medium spiny neurons via postsynaptic accumulation of high-conductance Ca2+-permeable AMPA receptors. This enhances reactivity to drug-associated cues and is required for the expression of incubation. Additionally, incubation of cocaine craving is associated with loss of the synaptic depression normally triggered by stimulation of metabotropic glutamate receptor 5 (mGlu5), leading to endocannabinoid production, and expressed presynaptically via cannabinoid receptor 1 activation. Previous studies have found alterations in mGlu5 and Homer proteins associated with the loss of this synaptic depression. Here we conducted coimmunoprecipitation studies to investigate associ...

Two novel short-interval intracortical inhibition (SICI) protocols, assessing SICI across a range of interstimulus intervals (ISIs) using either parallel threshold-tracking transcranial magnetic stimulation (TT-TMS) or automated conventional TMS (cTMS), were recently introduced. However, the test-retest reliability of these protocols has not been investigated, which is important if they are to be introduced in the clinic. SICI was recorded in 18 healthy subjects using TT-TMS (T-SICI) and cTMS (A-SICI). All subjects were examined at four identical sessions, i.e., morning and afternoon sessions on 2 d, 5–7 d apart. Both SICI protocols were performed twice at each session by the same observer. In one of the sessions, another observer performed additional examinations. Neither intraobserver nor interobserver measures of SICI differed significantly between examinations, except for T-SICI at ISI 3 ms ( p  = 0.00035) and A-SICI at ISI 2.5 ms ( p  = 0.0103). Intraday reliability was poor-to-good for A-SICI and mod...

Normal aging is associated with a decline in memory and motor learning ability. However, the exact form of these impairments (e.g., the short-term temporal stability and affected learning mechanisms) is largely unknown. Here, we used a sensorimotor adaptation task to examine changes in the temporal stability of two forms of learning (explicit and implicit) because of normal aging. Healthy young subjects (age range, 19–28 years; 20 individuals) and older human subjects (age range, 63–85 years; 19 individuals) made reaching movements in response to altered visual feedback. On each trial, subjects turned a rotation dial to select an explicit aiming direction. Once selected, the display was removed and subjects moved the cursor from the start position to the target. After initial training with the rotational feedback perturbation, subjects completed a series of probe trials at different delay periods to systematically assess the short-term retention of learning. For both groups, the explicit aiming showed no s...

The ability to learn dexterous motor skills is a fundamental aspect of human behavior. However, the underlying neural circuit mechanisms for dexterous skill learning are unclear. Advancing our understanding of motor skill learning requires the integration of modern neuroscientific techniques with a rigorously characterized dexterous task. The development of automated rodent skilled reaching with paw tracking allows detailed analysis of how reach-to-grasp kinematics evolve during learning. We assessed how both “gross” forelimb and “fine” digit kinematics changed as rats learned skilled reaching. Rats whose success rates increased (learners) consistently reduced the variability in their reach trajectories. Refinement of fine digit control generally continued after consistency in gross hand transport to the pellet plateaued. Interestingly, most rats whose success rates did not increase (non-learners) also converged on consistent reach kinematics. Some non-learners, however, maintained substantial variability ...

The V-ATPase is a highly conserved enzymatic complex that ensures appropriate levels of organelle acidification in virtually all eukaryotic cells. While the general mechanisms of this proton pump have been well studied, little is known about the specific regulations of neuronal V-ATPase. Here, we studied CG31030, a previously uncharacterized Drosophila protein predicted from its sequence homology to be part of the V-ATPase family. In contrast to its ortholog ATP6AP1/VhaAC45 which is ubiquitous, we observed that CG31030 expression is apparently restricted to all neurons, and using CRISPR/Cas9-mediated gene tagging, that it is mainly addressed to synaptic terminals. In addition, we observed that CG31030 is essential for fly survival and that this protein co-immunoprecipitates with identified V-ATPase subunits, and in particular ATP6AP2. Using a genetically-encoded pH probe (VMAT-pHluorin) and electrophysiological recordings at the larval neuromuscular junction, we show that CG31030 knock-down induces a major...

Forming long-term memories is crucial for adaptive behavior and survival in changing environments. The molecular consolidation processes which underlie the formation of these long-term memories are dependent on protein synthesis in excitatory and SST-expressing neurons. A centrally important, parallel process to this involves the removal of the memory constraint quinone reductase 2 (QR2), which has been recently shown to enhance memory consolidation for novel experiences in the cortex and hippocampus, via redox modulation. However, it is unknown within which cell type in the cortex removal of QR2 occurs, nor how this affects neuronal function. Here, we use novel taste learning in the mouse anterior insular cortex (aIC) to show that similarly to mRNA translation, QR2 removal occurs in excitatory and SST-expressing neurons. Interestingly, both novel taste and QR2 inhibition reduce excitability specifically within SST, but not excitatory neurons. Furthermore, reducing QR2 expression in SST, but not in PV or e...

The opioid epidemic led to an increase in the number of neonatal opioid withdrawal syndrome (NOWS) cases in infants born to opioid-dependent mothers. Hallmark features of NOWS include weight loss, severe irritability, respiratory problems, and sleep fragmentation. Mouse models provide an opportunity to identify brain mechanisms that contribute to NOWS. Neonatal outbred Swiss Webster Cartworth Farms White (CFW) mice were administered morphine (15 mg/kg, s.c.) twice daily from postnatal day 1 (P1) to P14, an approximation of the third trimester of human gestation. Female and male mice underwent behavioral testing on P7 and P14 to determine the impact of opioid exposure on anxiety and pain sensitivity. Ultrasonic vocalizations (USVs) and daily body weights were also recorded. Brainstems containing pons and medulla were collected during morphine withdrawal on P14 for RNA sequencing. Morphine induced weight loss from P2 to P14, which persisted during adolescence (P21) and adulthood (P50). USVs markedly increase...