Biology subjects

Wickens, J. R.

Publications and source records attributed to Wickens, J. R..

5 recordsLinked to original sources

bioRxiv2024

Acute drug induced parkinsonian akinesia is associated with reduced rate and increased regularity of neuronal activity in the pedunculopontine tegmental nucleus of unanesthetized rats

The pedunculopontine tegmental nucleus of the brainstem is important for a wide range of functions, including sensorimotor integration and regulation of locomotion and discrete forelimb movements. Evidence suggests it is structurally disordered as part of the neuropathology of the movement disorder Parkinsons disease. To assess whether neuronal activity is also affected in parkinsonian model animals we used single neuron recordings in free moving rats to determine the effects of acute drug-induced parkinsonism on the firing rate of the neurons. Acute parkinsonian akinesia was associated with reduction in resting firing rate and increased firing regularity, consistent with reduced excitability in this state.

neuroscience↗

bioRxiv2022

Mechanism of dopamine traveling waves in the striatum: theory and experiment

Striatal dopamine (DA) encodes reward, with recent work showing that DA release occurs in spatiotemporal waves. However, the mechanism of DA waves is unknown. Here we report that the striatal cholinergic neuropil also exhibits wave-like activity, and that the spatial scale of striatal DA release is extended by nicotinic receptors. Based on these findings we hypothesized that the local reciprocal interaction between cholinergic interneurons (CIN) and DA axons suffices to drive endogenous traveling waves. We show that the morphological and physiological properties of the CIN-DA interaction can be modeled as a reaction-diffusion system that gives rise to traveling waves. Analytically-tractable versions of the model show that the structure and the nature of propagation of CIN and DA traveling waves depend on their coupling, and that traveling waves can give rise to empirically observed correlations between these signals. Our model provides a biophysical mechanism for wave formation and predicts that the observed DA and CIN waves are strongly coupled phenomena.

neuroscience↗

bioRxiv2022

Ventral motor thalamic input to prelimbic cortex, but not to striatum, mediates cost-benefit decision-making in rats

Corticostriatal neurons in prelimbic cortex contribute to decisions that require a trade-off between cost and benefit. The ventral motor thalamus sends dense projections to many cortical areas, including the prelimbic cortex. We investigated whether this input from the ventral motor thalamus to prelimbic cortex contributes to cost-benefit decision-making. Optogenetic inhibition of ventral motor thalamic axon terminals in prelimbic cortex biased rats towards a high cost-high benefit option and, in anesthetized rats, decreased neuronal activity in deep layers of prelimbic cortex. Stimulation of ventral motor thalamic nuclei induced a neuronal response in deep layers of prelimbic cortex and simultaneous optogenetic inhibition of layer 1 inhibitory interneurons similarly decreased neuronal activity. Our results indicate that ventral motor thalamic input to prelimbic cortex mediates cost-benefit decision-making. Significance StatementOur results indicate that ventral motor thalamic input to prelimbic cortex plays a critical role in decisions that require a trade-off between two conflicting reward values. Traditionally, ventral motor thalamic nuclei were primarily associated with motor control, but more recently these thalamic nuclei have been implicated in tasks that require animals to choose between two alternatives. Our results highlight the need to reevaluate the role of the ventral motor thalamic nuclei in cognition. Furthermore, prelimbic cortex and, more generally, prefrontal cortex have been associated with chronic stress and major depressive disorder, highlighting the possibility that ventral motor thalamic nuclei might be involved in these disorders.

neuroscience↗

bioRxiv2019

Coincidence of cholinergic pauses, dopaminergic activation and depolarization drives synaptic plasticity in the striatum

Pauses in the firing of tonically-active cholinergic interneurons (ChIs) in the striatum coincide with phasic activation of dopamine neurons during reinforcement learning. However, how this pause influences cellular substrates of learning is unclear. Using two in vivo paradigms, we report that long-term potentiation (LTP) at corticostriatal synapses with spiny projection neurons (SPNs) is dependent on the temporal coincidence of ChI pause and dopamine phasic activation, critically accompanied by SPN depolarization.

neuroscience↗

bioRxiv2019

Anterior corpus callosum modulates symmetric forelimb movements during spontaneous food handling behavior of rats.

Bimanual motor actions, such as threading a needle, require coordination of the movements of each hand according to the state of the other hand. By connecting homologous cortical regions between the two cerebral hemispheres, the corpus callosum is thought to play a key role in such bimanual coordination. However, direct experimental evidence of the contribution of the corpus callosum to natural behaviors requiring bimanual coordination, such as feeding, is lacking. We investigated the hypothesis that the corpus callosum mediates bimanual movements during food-handling behavior. We first traced the forelimb-related components of the motor corpus callosum in Long-Evans rats, and found that the callosal fiber bundle from the forelimb motor areas passes through the anterior part of the corpus callosum. We then confirmed by electrophysiological recordings that blocking the axonal conduction of fibers in the anterior corpus callosum reduced neural transmission between cortical forelimb areas. The causal role of corpus callosum in bimanual coordination was then tested by analyzing forelimb kinematics during object manipulation, before and after blocking axonal conduction in the anterior corpus callosum. We found the frequency of occurrence of symmetric bimanual movements was reduced by inhibition of anterior corpus callosum. In contrast, asymmetric bimanual movement was increased. Our findings suggest that the anterior corpus callosum coordinates the direction of bimanual movement.

neuroscience↗