Distributed Network Actions by Nicotine Increase the Threshold for Spike-Timing-Dependent Plasticity in Prefrontal Cortex

SummaryNicotine enhances attention and working memory by activating nicotinic acetylcholine receptors (nAChRs). The prefrontal cortex (PFC) is critical for these cognitive functions and is also rich in nAChR expression. Specific cellular and synaptic mechanisms underlying nicotine's effects on cognition remain elusive. Here we show that nicotine exposure increases the threshold for synaptic spike-timing-dependent potentiation (STDP) in layer V pyramidal neurons of the mouse PFC. During coincident presynaptic and postsynaptic activity, nicotine reduces dendritic calcium signals associated with action potential propagation by enhancing GABAergic transmission. This results from a series of presynaptic actions involving different PFC interneurons and multiple nAChR subtypes. Pharmacological block of nAChRs or GABAA receptors prevented nicotine's actions and restored STDP, as did increasing dendritic calcium signals with stronger postsynaptic activity. Thus, by activating nAChRs distributed throughout the PFC neuronal network, nicotine affects PFC information processing and storage by increasing the amount of postsynaptic activity necessary to induce STDP

Neuromodulation of Spike-Timing-Dependent Plasticity: Past, Present, and Future.

Spike-timing-dependent synaptic plasticity (STDP) is a leading cellular model for behavioral learning and memory with rich computational properties. However, the relationship between the millisecond-precision spike timing required for STDP and the much slower timescales of behavioral learning is not well understood. Neuromodulation offers an attractive mechanism to connect these different timescales, and there is now strong experimental evidence that STDP is under neuromodulatory control by acetylcholine, monoamines, and other signaling molecules. Here, we review neuromodulation of STDP, the underlying mechanisms, functional implications, and possible involvement in brain disorders.BBSR

Integration of Spiking Neural Networks for Understanding Interval Timing

The ability to perceive the passage of time in the seconds-to-minutes range is a vital and ubiquitous characteristic of life. This ability allows organisms to make behavioral changes based on the temporal contingencies between stimuli and the potential rewards they predict. While the psychophysical manifestations of time perception have been well-characterized, many aspects of its underlying biology are still poorly understood. A major contributor to this is limitations of current in vivo techniques that do not allow for proper assessment of the di signaling over micro-, meso- and macroscopic spatial scales. Alternatively, the integration of biologically inspired artificial neural networks (ANNs) based on the dynamics and cyto-architecture of brain regions associated with time perception can help mitigate these limitations and, in conjunction, provide a powerful tool for progressing research in the field. To this end, this chapter aims to: (1) provide insight into the biological complexity of interval timing, (2) outline limitations in our ability to accurately assess these neural mechanisms in vivo, and (3) demonstrate potential application of ANNs for better understanding the biological underpinnings of temporal processing

Variability in non-invasive brain stimulation studies: reasons and results

Non-invasive brain stimulation techniques (NIBS), such as Theta Burst Stimulation (TBS), Paired Associative Stimulation (PAS) and transcranial Direct Current Stimulation (tDCS), are widely used to probe plasticity in the human motor cortex (M1). Although TBS, PAS and tDCS differ in terms of physiological mechanisms responsible for experimentally-induced cortical plasticity, they all share the ability to elicit long-term potentiation (LTP) and depression (LTD) in M1. However, NIBS techniques are all affected by relevant variability in intra- and inter-subject responses. A growing number of factors contributing to NIBS variability have been recently identified and reported. In this review, we have readdressed the issue of variability in human NIBS studies. We have first briefly discussed the physiological mechanisms responsible for TBS, PAS and tDCS-induced cortical plasticity. Then, we have provided statistical measures of intra- and inter-subject variability, as calculated in previous studies. Finally, we have reported in detail known sources of variability by categorizing them into physiological, technical and statistical factors. Improving knowledge about sources of variability could lead to relevant advances in designing new tailored NIBS protocols in physiological and pathological conditions

Primate pre-arcuate cortex actively maintains persistent representations of saccades from plans to outcomes

Dorso-lateral prefrontal cortex is thought to contribute to adaptive behavior by integrating temporally dispersed, behaviorally-relevant factors. Past work has revealed a variety of neural representations preceding actions, which are involved in internal processes like planning, working memory and covert attention. Task-related activity following actions has often been reported, but so far lacks a clear interpretation. We leveraged modified versions of classic oculomotor paradigms and population recordings to show that post-saccadic activity is a dominant signal in dorso-lateral prefrontal cortex that is distinct from pre-saccadic activity. Unlike pre-saccadic activity, post-saccadic activity occurs after each saccade, although its strength and duration are modulated by task context and expected rewards. In contrast to representations preceding actions, which appear to be mixed randomly across neurons, post-saccadic activity results in representations that are highly structured at the single-neuron and population level. Overall, the properties of post-saccadic activity are consistent with those of an action memory, an internal process with a possible role in learning and updating spatial representations

Cortico-spinal modularity in the parieto-frontal system: a new perspective on action control

: Classical neurophysiology suggests that the motor cortex (MI) has a unique role in action control. In contrast, this review presents evidence for multiple parieto-frontal spinal command modules that can bypass MI. Five observations support this modular perspective: (i) the statistics of cortical connectivity demonstrate functionally-related clusters of cortical areas, defining functional modules in the premotor, cingulate, and parietal cortices; (ii) different corticospinal pathways originate from the above areas, each with a distinct range of conduction velocities; (iii) the activation time of each module varies depending on task, and different modules can be activated simultaneously; (iv) a modular architecture with direct motor output is faster and less metabolically expensive than an architecture that relies on MI, given the slow connections between MI and other cortical areas; (v) lesions of the areas composing parieto-frontal modules have different effects from lesions of MI. Here we provide examples of six cortico-spinal modules and functions they subserve: module 1) arm reaching, tool use and object construction; module 2) spatial navigation and locomotion; module 3) grasping and observation of hand and mouth actions; module 4) action initiation, motor sequences, time encoding; module 5) conditional motor association and learning, action plan switching and action inhibition; module 6) planning defensive actions. These modules can serve as a library of tools to be recombined when faced with novel tasks, and MI might serve as a recombinatory hub. In conclusion, the availability of locally-stored information and multiple outflow paths supports the physiological plausibility of the proposed modular perspective

Paired Associative Stimulation drives the emergence of motor resonance

Abstract Background Associative plasticity, the neurophysiological bases of Hebbian learning, has been implied in the formation of the association between sensory and motor representations of actions in the Mirror Neuron System; however, such inductor role still needs empirical support. Objective/hypothesis We have assessed whether Paired Associative Stimulation (PAS), known to activate Hebbian associative plasticity, can induce the formation of atypical (absent in normal conditions), visuo-motor associations, reshaping motor resonance. Methods Healthy participants underwent a novel PAS protocol (mirror-PAS, m-PAS), during which they were exposed to repeated pairings of transcranial magnetic stimulation (TMS) applied over the right primary motor cortex (M1), time-locked with the view of index-finger movements of the right (ipsilateral) hand. In a first experiment, the inter-stimulus interval (ISI) between visual-action stimuli and TMS pulses was varied. Before and after each m-PAS session, motor resonance was assessed by recording Motor Evoked Potentials induced by single-pulse TMS applied to the right M1, during the observation of both contralateral (left) and ipsilateral (right) index-finger movements. In the second experiment, the specificity of the m-PAS was assessed by presenting a visual stimulus depicting a non-biological movement. Results Before m-PAS, the facilitation of corticospinal excitability occurred only during the view of contralateral (with respect to the TMS side) index-finger movements. The m-PAS induced new ipsilateral motor resonance responses, indexed by atypical facilitation of corticospinal excitability by the view of ipsilateral hand movements. This effect occurred only if the associative stimulation followed the chronometry of motor control (ISI of 25 ms) and if the visual stimulus of the m-PAS depicts a biological movement (human hand action). Conclusions The present findings provide the first empirical evidence that Hebbian learning induced by a PAS protocol shapes the visual-motor matching properties of the human Mirror Neuron System

Chapter Sleep Spindles – As a Biomarker of Brain Function and Plasticity

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