Biology subjects

Wiskerke, J.

Publications and source records attributed to Wiskerke, J..

5 recordsLinked to original sources

bioRxiv2026

Partial overlap in the symptom profile induced by microglia activation and systemic inflammation

Microglial activation is a common feature of neurological and inflammatory diseases and may contribute to some associated symptoms. However, methodological limitations have made it challenging to identify the specific symptoms and behavioral consequences of selective microglial activation. In this study, we examined the spectrum of symptoms elicited by acute chemogenetic activation of microglia in mice and compared them to those induced by endotoxin-driven systemic inflammation. Both interventions upregulated inflammatory gene expression in the brain, reduced voluntary wheel running, and decreased self-care. Systemic inflammation additionally caused anorexia, weight loss, reduced motivation to work for palatable food, and impaired motor performance in the rotarod test--effects not observed with chemogenetic microglial activation. By showing that acute microglial activation reproduces certain motivational aspects of the sickness response while sparing other functions, the findings might shed new light on the contribution of microglia to symptoms and behavioral alterations during disease.

neuroscience↗

bioRxiv2024

Melanocortin 4 receptor-expressing neurons in the lateral stripe of the striatum are involved in affect regulation and motor control

The dopaminergic system is crucial for affect regulation. Melanocortin 4 receptors (MC4R) in the ventral striatum have been shown to be necessary for establishing aversive states. Here, we set out to functionally characterize MC4R-expressing striatal neurons. MC4Rs were enriched in atypical Dopamine receptor 1 (D1) neurons in the lateral stripe of the striatum (LSS), an understudied area in the ventrolateral striatum. Fiber photometry recordings showed that MC4R neuron activity and local dopamine release in the LSS were increased by rewarding as well as aversive stimuli. Moreover, MC4R neuronal activity and glutamate release correlated strongly to body movement. Optogenetic activation of MC4R-LSS neurons was rewarding in a real-time place preference test and a self-stimulation paradigm, increased locomotor activity and induced striatal dopamine release. Collectively, our findings suggest that MC4R-LSS neurons are activated by salient stimuli of both rewarding and aversive character and that they induce positive affect, dopamine release and locomotion.

neuroscience↗

bioRxiv2018

The orexin-1 receptor antagonist SB-334867 reduces motivation, but not inhibitory control, in a rat stop signal task

There is considerable clinical interest in the neuropeptide orexin/hypocretin for its ability to regulate motivation and reward as well as arousal and wakefulness. For instance, antagonists for the orexin-1 receptor (OxR1) are thought to hold great promise for treating drug addiction and disorders associated with overeating, as these compounds repeatedly have been found to suppress seeking of various drugs of abuse as well as highly palatable foods in preclinical models. Given the hypothesized role of OxR1 signaling in cue-driven motivation, an outstanding question is whether pharmacologically blocking this receptor affects cognitive functioning. Response inhibition - the ability to cancel ongoing behavior - is one aspect of cognitive control that may be particularly relevant. Response inhibition deficits are commonly associated with a range of psychiatric disorders and neurological diseases, including substance use disorders and obesity. Moreover, OxR1 signaling recently has been implicated in waiting impulsivity, another aspect of inhibitory control. Here, we investigated the effects of the OxR1 antagonist SB-334867 on response inhibition in a rat version of the stop signal reaction time task. Results show that acutely blocking OxR1 had minimal effects on response inhibition or attentional functioning. In contrast, this manipulation reduced motivation to perform the task and earn food rewards. These results add to the growing body of literature implicating OxR1 in the regulation of motivation and suggest that effects of pharmacological compounds such as SB-334867 on drug seeking behavior are not related to effects on response inhibition.\n\nHighlightsO_LIOrexin-1 receptor antagonists hold great promise for treatment of drug addiction\nC_LIO_LIThese compounds are thought to reduce motivation for drug seeking\nC_LIO_LILess is known about effects of orexin-1 receptor blockade on cognitive functioning\nC_LIO_LIWe tested the orexin-1 receptor antagonist SB-334867 in a rat stop signal task\nC_LIO_LISB-334867 reduced task motivation but had little effect on executive control as measured with response inhibition\nC_LI

neuroscience↗

bioRxiv2018

Opposing Influence of Sensory and Motor Cortex on Striatal Circuitry and Choice Behavior

The striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1- or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV interneurons. Optogenetic stimulation of M1 afferents produced the opposite behavioral effect. Thus, our results suggest opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry.

neuroscience↗

bioRxiv2018

Camouflaging of repetitive movements in autistic female and transgender adults

Repetitive movements (RMs), colloquially called \"stimming\" among adult autistic people and \"motor stereotypies\" among scientists, are common in autism. These behaviors fall under the domain of restricted and repetitive behaviors in the current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). RMs can be socially disruptive or cause self-harm, but can also be experienced as cognitively or emotionally helpful and even enjoyable. Overt RMs are less common in females than in males, which could contribute to clinical difficulties in detecting their autism. In the social domain, autistic people with intact intelligence can often mask their social difficulties through various compensation strategies, and females appear especially skilled at it. Subjective report from verbally able adults may be useful as a first step in detecting potential camouflaging of RMs, and to provide a foundation for further studies. We founded an Internet-based outreach platform that became particularly successful in reaching female and transgender individuals. We recruited 342 individuals to an anonymous online questionnaire, collected data about self-reported RMs and probed for potential camouflaging. The cohort comprised 56% formally diagnosed participants and 44% who self-identified as autistic, and 17% of all participants reported non-cisgender identity. Thus, in addition to diagnosed women, we reached two populations that would normally be excluded from autism studies: transgender and undiagnosed participants. We found high rates of RMs in both diagnosed and self-identifying participants, and a striking prevalence of camouflaging. We suggest that camouflaging of RMs may contribute to underdiagnosis of autism, at least in females and transgender people, and that further studies on this topic are exceptionally important.

neuroscience↗