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...

Information theoretic metrics have proven useful in quantifying the relationship between behaviorally relevant parameters and neuronal activity with relatively few assumptions. However, these metrics are typically applied to action potential (AP) recordings and were not designed for the slow timescales and variable amplitudes typical of functional fluorescence recordings (e.g., calcium imaging). The lack of research guidelines on how to apply and interpret these metrics with fluorescence traces means the neuroscience community has yet to realize the power of information theoretic metrics. Here, we used computational methods to create mock AP traces with known amounts of information. From these, we generated fluorescence traces and examined the ability of different information metrics to recover the known information values. We provide guidelines for how to use information metrics when applying them to functional fluorescence and demonstrate their appropriate application to GCaMP6f population recordings fro...

Psychostimulants such as amphetamine (AMPH) target dopamine (DA) neuron synapses to engender drug-induced plasticity. While DA neurons modulate the activity of striatal (Str) cholinergic interneurons (ChIs) with regional heterogeneity, how AMPH affects ChI activity has not been elucidated. Here, we applied quantitative fluorescence imaging approaches to map the dose-dependent effects of a single dose of AMPH on ChI activity at 2.5 and 24 h after injection across the mouse Str using the activity-dependent marker phosphorylated ribosomal protein S6 (p-rpS6240/244). AMPH did not affect the distribution or morphology of ChIs in any Str subregion. While AMPH at either dose had no effect on ChI activity after 2.5 h, ChI activity was dose dependently reduced after 24 h specifically in the ventral Str/nucleus accumbens (NAc), a critical site of psychostimulant action. AMPH at either dose did not affect the spontaneous firing of ChIs. Altogether this work demonstrates that a single dose of AMPH has delayed regional...

Recent evidence suggests that alteration of axon initial segment (AIS) geometry (i.e., length or location along the axon) contributes to CNS dysfunction in neurological diseases. For example, AIS length is shorter in the prefrontal cortex of type 2 diabetic mice with cognitive impairment. To determine the key type 2 diabetes-related factor that produces AIS shortening we modified levels of insulin, glucose, or the reactive glucose metabolite methylglyoxal in cultures of dissociated cortices from male and female mice and quantified AIS geometry using immunofluorescent imaging of the AIS proteins AnkyrinG and βIV spectrin. Neither insulin nor glucose modification altered AIS length. Exposure to 100 but not 1 or 10 μm methylglyoxal for 24 h resulted in accumulation of the methylglyoxal-derived advanced glycation end-product hydroimidazolone and produced reversible AIS shortening without cell death. Methylglyoxal-evoked AIS shortening occurred in both excitatory and putative inhibitory neuron populations and i...

Prolonged exposure to a stimulus causes desensitization of cortical neurons and results in perceptual changes. One example of this phenomenon is contrast adaptation, in which perceived differences between light and dark regions of a stimulus decrease. Blakemore, Muncey, and Ridley reported evidence for the “perceptual fading of a stabilized cortical image” in a 1971 Nature paper. Our goal was to replicate their second experiment, in which adaptation was measured across many contrasts, and develop an active learning exercise for undergraduate students. The experiment was coded using an open-source python package and psychophysical data were collected from two observers. On each trial, a sinusoidally modulated luminance grating appeared above fixation, and the task of the observer was to adjust the contrast of a grating below fixation until the two appeared identical. Between trials in the adaptation condition, a high contrast grating was presented in the top location; no such grating appeared between trials...

Dopaminergic modulation is essential for the control of voluntary movement; however, the role of dopamine in regulating the neural excitability of the primary motor cortex (M1) is not well understood. Here, we investigated two modes by which dopamine influences the input/output function of M1 neurons. To test the direct regulation of M1 neurons by dopamine, we performed whole-cell recordings of excitatory neurons and measured excitability before and after local, acute dopamine receptor blockade. We then determined whether chronic depletion of dopaminergic input to the entire motor circuit, via a mouse model of Parkinson’s disease, was sufficient to shift M1 neuron excitability. We show that D1 receptor (D1R) and D2R antagonism altered subthreshold and suprathreshold properties of M1 pyramidal neurons in a layer-specific fashion. The effects of D1R antagonism were primarily driven by changes to intrinsic properties, while the excitability shifts following D2R antagonism relied on synaptic transmission. In c...

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...

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...

Gustometers have made it possible to deliver liquids in functional magnetic resonance imaging (fMRI) settings for decades, and mouthpieces are a critical part of these taste delivery systems. Here, we propose an innovative 3D-printed fMRI mouthpiece inspired by children’s pacifiers, allowing human participants to swallow while lying down in an MRI scanner. We used a large sample to validate the effectiveness of our method. The results suggest that the mouthpiece can be used to deliver taste stimuli by showing significant clusters of activation in the insular and piriform cortex, which are regions that have been consistently identified in taste processing. This mouthpiece fulfills several criteria guaranteeing a gustatory stimulus of quality, making the delivery precise and reliable. Moreover, this new pacifier-shaped design is simple and cheap to manufacture, hygienic, comfortable to keep in the mouth, and flexible to use in diverse cases. We hope that this new method will promote and facilitate the study ...