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1. Epidural cerebellar stimulation drives widespread neural synchrony in the intact and stroke perilesional cortex.

   https://doi.org/10.1186/s12984-021-00881-9  

   Abbasi, A.; Danielsen, N.P.; Leung, J.; Muhammad, A.K.M.G.; Patel, S.; Gulati, T. (May 2021, Journal of neuroengineering and rehabilitation)

   Manto, Mario (Ed.)

   Background Cerebellar electrical stimulation has shown promise in improving motor recovery post-stroke in both rodent and human studies. Past studies have used motor evoked potentials (MEPs) to evaluate how cerebellar stimulation modulates ongoing activity in the cortex, but the underlying mechanisms are incompletely understood. Here we used invasive electrophysiological recordings from the intact and stroke-injured rodent primary motor cortex (M1) to assess how epidural cerebellar stimulation modulates neural dynamics at the level of single neurons as well as at the level of mesoscale dynamics. Methods We recorded single unit spiking and local field potentials (LFPs) in both the intact and acutely stroke-injured M1 contralateral to the stimulated cerebellum in adult Long-Evans rats under anesthesia. We analyzed changes in the firing rates of single units, the extent of synchronous spiking and power spectral density (PSD) changes in LFPs during and post-stimulation. Results Our results show that post-stimulation, the firing rates of a majority of M1 neurons changed significantly with respect to their baseline rates. These firing rate changes were diverse in character, as the firing rate of some neurons increased while others decreased. Additionally, these changes started to set in during stimulation. Furthermore, cross-correlation analysis showed a significant increase in coincident firing amongst neuronal pairs. Interestingly, this increase in synchrony was unrelated to the direction of firing rate change. We also found that neuronal ensembles derived through principal component analysis were more active post-stimulation. Lastly, these changes occurred without a significant change in the overall spectral power of LFPs post-stimulation. Conclusions Our results show that cerebellar stimulation caused significant, long-lasting changes in the activity patterns of M1 neurons by altering firing rates, boosting neural synchrony and increasing neuronal assemblies’ activation strength. Our study provides evidence that cerebellar stimulation can directly modulate cortical dynamics. Since these results are present in the perilesional cortex, our data might also help explain the facilitatory effects of cerebellar stimulation post-stroke. 

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2. Homeostatic regulation of extracellular signal-regulated kinase 1/2 activity and axonal Kv7.3 expression by prolonged blockade of hippocampal neuronal activity

   https://doi.org/10.3389/fncel.2022.838419  

   Baculis, Brian C.; Kesavan, Harish; Weiss, Amanda C.; Kim, Edward H.; Tracy, Gregory C.; Ouyang, Wenhao; Tsai, Nien-Pei; Chung, Hee Jung (July 2022, Frontiers in Cellular Neuroscience)

   Homeostatic plasticity encompasses the mechanisms by which neurons stabilize their synaptic strength and excitability in response to prolonged and destabilizing changes in their network activity. Prolonged activity blockade leads to homeostatic scaling of action potential (AP) firing rate in hippocampal neurons in part by decreased activity of N-Methyl-D-Aspartate receptors and subsequent transcriptional down-regulation of potassium channel genes includingKCNQ3which encodes K_v7.3. Neuronal K_v7 channels are mostly heterotetramers of K_v7.2 and K_v7.3 subunits and are highly enriched at the axon initial segment (AIS) where their current potently inhibits repetitive and burst firing of APs. However, whether a decrease in K_v7.3 expression occurs at the AIS during homeostatic scaling of intrinsic excitability and what signaling pathway reducesKCNQ3transcript upon prolonged activity blockade remain unknown. Here, we report that prolonged activity blockade in cultured hippocampal neurons reduces the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) followed by a decrease in the activation of brain-derived neurotrophic factor (BDNF) receptor, Tropomyosin receptor kinase B (TrkB). Furthermore, both prolonged activity blockade and prolonged pharmacological inhibition of ERK1/2 decreaseKCNQ3andBDNFtranscripts as well as the density of K_v7.3 and ankyrin-G at the AIS. Collectively, our findings suggest that a reduction in the ERK1/2 activity and subsequent transcriptional down-regulation may serve as a potential signaling pathway that links prolonged activity blockade to homeostatic control of BDNF-TrkB signaling and K_v7.3 density at the AIS during homeostatic scaling of AP firing rate. 

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3. Protosequences in brain organoids model intrinsic brain states

   https://doi.org/10.1101/2023.12.29.573646  

   van_der_Molen, Tjitse; Spaeth, Alex; Chini, Mattia; Hernandez, Sebastian; Kaurala, Gregory A; Schweiger, Hunter E; Duncan, Cole; McKenna, Sawyer; Geng, Jinghui; Lim, Max; et al (December 2023, bioRxiv)

   Abstract Neuronal firing sequences are thought to be the basic building blocks of neural coding and information broadcasting within the brain. However, when sequences emerge during neurodevelopment remains unknown. We demonstrate that structured firing sequences are present in spontaneous activity of human and murine brain organoids andex vivoneonatal brain slices from the murine somatosensory cortex. We observed a balance between temporally rigid and flexible firing patterns that are emergent phenomena in human and murine brain organoids and early postnatal murine somatosensory cortex, but not in primary dissociated cortical cultures. Our findings suggest that temporal sequences do not arise in an experience-dependent manner, but are rather constrained by an innate preconfigured architecture established during neurogenesis. These findings highlight the potential for brain organoids to further explore how exogenous inputs can be used to refine neuronal circuits and enable new studies into the genetic mechanisms that govern assembly of functional circuitry during early human brain development. 

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4. Optogenetic stimulation shifts the excitability of cerebral cortex from type I to type II: oscillation onset and wave propagation

   Heitmann, S.; Rule, M.; Truccolo, W.; Ermentrout, B. (January 2017, PLOS computational biology)

   Constant optogenetic stimulation targeting both pyramidal cells and inhibitory interneurons has recently been shown to elicit propagating waves of gamma-band (40–80 Hz) oscillations in the local field potential of non-human primate motor cortex. The oscillations emerge with non-zero frequency and small amplitude—the hallmark of a type II excitable medium—yet they also propagate far beyond the stimulation site in the manner of a type I excitable medium. How can neural tissue exhibit both type I and type II excitability? We investigated the apparent contradiction by modeling the cortex as a Wilson-Cowan neural field in which optogenetic stimulation was represented by an external current source. In the absence of any external current, the model operated as a type I excitable medium that supported propagating waves of gamma oscillations similar to those observed in vivo. Applying an external current to the population of inhibitory neurons transformed the model into a type II excitable medium. The findings suggest that cortical tissue normally operates as a type I excitable medium but it is locally transformed into a type II medium by optogenetic stimulation which predominantly targets inhibitory neurons. The proposed mechanism accounts for the graded emergence of gamma oscillations at the stimulation site while retaining propagating waves of gamma oscillations in the non-stimulated tissue. It also predicts that gamma waves can be emitted on every second cycle of a 100 Hz oscillation. That prediction was subsequently confirmed by re-analysis of the neurophysiological data. The model thus offers a theoretical account of how optogenetic stimulation alters the excitability of cortical neural fields. 

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5. Sparse Firing in a Hybrid Central Pattern Generator for Spinal Motor Circuits

   https://doi.org/10.1162/neco_a_01660  

   Strohmer, Beck; Najarro, Elias; Ausborn, Jessica; Berg, Rune W; Tolu, Silvia (April 2024, Neural Computation)

   Central pattern generators are circuits generating rhythmic movements, such as walking. The majority of existing computational models of these circuits produce antagonistic output where all neurons within a population spike with a broad burst at about the same neuronal phase with respect to network output. However, experimental recordings reveal that many neurons within these circuits fire sparsely, sometimes as rarely as once within a cycle. Here we address the sparse neuronal firing and develop a model to replicate the behavior of individual neurons within rhythm-generating populations to increase biological plausibility and facilitate new insights into the underlying mechanisms of rhythm generation. The developed network architecture is able to produce sparse firing of individual neurons, creating a novel implementation for exploring the contribution of network architecture on rhythmic output. Furthermore, the introduction of sparse firing of individual neurons within the rhythm-generating circuits is one of the factors that allows for a broad neuronal phase representation of firing at the population level. This moves the model toward recent experimental findings of evenly distributed neuronal firing across phases among individual spinal neurons. The network is tested by methodically iterating select parameters to gain an understanding of how connectivity and the interplay of excitation and inhibition influence the output. This knowledge can be applied in future studies to implement a biologically plausible rhythm-generating circuit for testing biological hypotheses. 

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