Adaptive behavior requires the ability to appropriately react to action errors. Post-error slowing of response times (PES) is one of the most reliable phenomena in human behavior. It has been proposed that PES is partially achieved through inhibition of the motor system. However, there is no direct evidence for this link – or indeed, that the motor system is physiologically inhibited after errors altogether. Here, we used transcranial magnetic stimulation and electromyography to measure cortico-spinal excitability (CSE) across four experiments using a Simon task, in which female and male human participants sometimes committed errors. Errors were followed by reduced CSE at two different time points and in two different modes. Shortly after error commission (250ms) CSE was broadly suppressed – i.e., even task-unrelated motor effectors were inhibited. During the preparation of the subsequent response, CSE was specifically reduced at task-relevant effectors only. This latter effect was directly related to PES,...

Forgetting is important for animals to manage acquired memories to enable adaptation to changing environments; however, the neural network in mechanisms of forgetting is not fully understood. To understand the mechanisms underlying forgetting, we examined olfactory adaptation, a form of associative learning, in Caenorhabditis elegans ( C. elegans ). The forgetting of diacetyl olfactory adaptation in C. elegans is regulated by secreted signals from AWC sensory neurons via the TIR-1/JNK-1 pathway. These signals cause a decline of the sensory memory trace in AWA neurons where diacetyl is mainly sensed. To further understand the neural network that regulates this forgetting, we investigated the function of interneurons downstream of AWA and AWC neurons. We found that a pair of interneurons, AIA, is indispensable for the proper regulation of behavioral forgetting of diacetyl olfactory adaptation. Loss of or inactivation of AIA caused the impairment of the chemotaxis recovery after adaptation without causing sev...

The habenula is an evolutionarily conserved structure of the vertebrate brain that is essential for behavioural flexibility and mood control. It is spontaneously active and is able to access diverse states when the animal is exposed to sensory stimuli. Here we investigate the dynamics of habenula spontaneous activity, to gain insight into how sensitivity is optimized. Two-photon calcium imaging was performed in resting zebrafish larvae at single cell resolution. An analysis of avalanches of inferred spikes suggests that the habenula is subcritical. Activity had low covariance and a small mean, arguing against dynamic criticality. A multiple regression estimator of autocorrelation time suggests that the habenula is neither fully asynchronous nor perfectly critical, but is reverberating. This pattern of dynamics may enable integration of information and high flexibility in the tuning of network properties, thus providing a potential mechanism for the optimal responses to a changing environment. Significance...

Feature selectivity of visual cortical responses measured during passive fixation provides only a partial view of selectivity because it does not account for the influence of cognitive factors. Here we focus on primate area V4 and ask how neuronal tuning is modulated by task engagement. We investigated whether responses to colored shapes during active shape discrimination are simple, stimulus-agnostic, scaled versions of responses during passive fixation, akin to results from attentional studies. Alternatively, responses could be subject to stimulus-specific scaling, that is, responses to different stimuli are modulated differently, resulting in changes in underlying shape/color selectivity. Among 83 well-isolated V4 neurons in two male macaques, only a minority (16 of 83), which were weakly tuned to both shape and color, displayed responses during fixation and discrimination tasks that could be related by stimulus-agnostic scaling. The majority (67 of 83), which were strongly tuned to shape, color, or bot...

Reward motivation enhances memory through interactions between mesolimbic, hippocampal, and cortical systems, both during and after encoding. Developmental changes in these distributed neural circuits may lead to age-related differences in reward-motivated memory and the underlying neural mechanisms. Converging evidence from cross-species studies suggests that subcortical dopamine signaling is increased during adolescence, which may lead to stronger memory representations of rewarding, relative to mundane, events and changes in the contributions of underlying subcortical and cortical brain mechanisms across age. Here, we used fMRI to examine how reward motivation influences the “online” encoding and “offline” postencoding brain mechanisms that support long-term associative memory from childhood to adulthood in human participants of both sexes. We found that reward motivation led to both age-invariant enhancements and nonlinear age-related differences in associative memory after 24 h. Furthermore, reward-re...

Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult male and female primary visual cortex in the MECP2-duplication syndrome animal model of autism. Increased response reliability was due in part to decreased response amplitude, decreased fluctuations in endogenous activity, and an abnormal decoupling of visual-evoked activity from endogenous activity. Similar to what was observed neuronally, the optokinetic reflex occurred more reliably at low contrasts in mutant mice compared with controls. Retinal responses did not explain our observations. These data suggest that the circuit mechanisms for combining sensory-evoked and endogenous signal and noise processes may be altered in this for...

The human dorsolateral prefrontal cortex (DLPFC) has long captured the attention of neuroscientists because of the diversity of the cognitive functions it supports. Its involvement has been shown in a variety of executive functions such as abstract reasoning ([Bernardi et al., 2020][1]), response

The olfactory sense of the domestic dog is widely recognized as being highly sensitive with a diverse function; however, little is known about the structure of its olfactory system. This study examined a cohort of mixed-sex mesaticephalic canines and used diffusion tensor imaging (DTI), an MRI technique, to map connections from the olfactory bulb to other cortical regions of the brain. The results were validated using the Klingler dissection method. An extensive pathway composed of five white matter tracts connecting to the occipital lobe, cortical spinal tract, limbic system, piriform lobe, and entorhinal pathway was identified. This is the first documentation of a direct connection between the olfactory bulb and occipital lobe in any species and is a step toward further understanding how the dog integrates olfactory stimuli into their cognitive function. SIGNIFICANCE STATEMENT The highly sensitive olfactory system of the domestic dog is largely unexplored. We applied diffusion tractography and dissectio...

Adam Davison, Uwe Thorsten Lux, Johann Helmut Brandstätter, Norbert Babai (see pages [6325–6343][1]) Cone photoreceptors are hyperpolarized in light and become depolarized as the light dims. The depolarization spreads passively to the axon terminal, where it causes voltage-activated calcium

While effective in treating abdominal pain, opioids have significant side effects. Recent legalization of cannabis will likely promote use of cannabinoids as an adjunct or alternative to opioids, despite a lack of evidence. We aimed to investigate whether cannabinoids inhibit mouse colonic nociception, alone or in combination with opioids at low doses. Experiments were performed on C57BL/6 male and female mice. Visceral nociception was evaluated by measuring visceromotor responses (VMR), afferent nerve mechanosensitivity in flat-sheet colon preparations, and excitability of isolated DRG neurons. Blood oxygen saturation, locomotion, and defecation were measured to evaluate side effects. An agonist of cannabinoid 1 receptor (CB1R), arachidonyl-2′-chloroethylamide (ACEA), dose-dependently decreased VMR. ACEA and HU-210 (another CB1R agonist) also attenuated colonic afferent nerve mechanosensitivity. Additionally, HU-210 concentration-dependently decreased DRG neuron excitability, which was reversed by the CB1...