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1. Switching neuron contributions to second network activity

   https://doi.org/10.1152/jn.00373.2023  

   Fahoum, Savanna-Rae H.; Blitz, Dawn M. (February 2024, Journal of Neurophysiology)

   Network flexibility is important for adaptable behaviors. This includes neuronal switching, where neurons alter their network participation, including changing from single- to dual-network activity. Understanding the implications of neuronal switching requires determining how a switching neuron interacts with each of its networks. Here, we tested 1) whether “home” and second networks, operating via divergent rhythm generation mechanisms, regulate a switching neuron, and 2) if a switching neuron, recruited via modulation of intrinsic properties, contributes to rhythm or pattern generation in a new network. Small, well-characterized feeding-related networks (pyloric, ~1 Hz; gastric mill, ~0.1 Hz) and identified modulatory inputs make the isolated crab (Cancer borealis) stomatogastric nervous system (STNS) a useful model to study neuronal switching. In particular, the neuropeptide Gly1-SIFamide switches the lateral posterior gastric (LPG) neuron (2 copies) from pyloric-only to dual-frequency pyloric/gastric mill (fast/slow) activity via modulation of LPG intrinsic properties. Using current injections to manipulate neuronal activity, we found that gastric mill, but not pyloric, network neurons regulated the intrinsically generated LPG slow bursting. Conversely, selective elimination of LPG from both networks using photoinactivation revealed that LPG regulated gastric mill neuron firing frequencies but was not necessary for gastric mill rhythm generation or coordination. However, LPG alone was sufficient to produce a distinct pattern of network coordination. Thus, modulated intrinsic properties underlying dual-network participation may constrain which networks can regulate switching neuron activity. Further, recruitment via intrinsic properties may occur in modulatory states where it is important for the switching neuron to actively contribute to network output. 

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2. State-dependent activity dynamics of hypothalamic stress effector neurons

   https://doi.org/10.7554/eLife.76832  

   Ichiyama, Aoi; Mestern, Samuel; Benigno, Gabriel B; Scott, Kaela E; Allman, Brian L; Muller, Lyle; Inoue, Wataru (June 2022, eLife)

   The stress response necessitates an immediate boost in vital physiological functions from their homeostatic operation to an elevated emergency response. However, the neural mechanisms underlying this state-dependent change remain largely unknown. Using a combination of in vivo and ex vivo electrophysiology with computational modeling, we report that corticotropin releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN), the effector neurons of hormonal stress response, rapidly transition between distinct activity states through recurrent inhibition. Specifically, in vivo optrode recording shows that under non-stress conditions, CRH PVN neurons often fire with rhythmic brief bursts (RB), which, somewhat counterintuitively, constrains firing rate due to long (~2 s) interburst intervals. Stressful stimuli rapidly switch RB to continuous single spiking (SS), permitting a large increase in firing rate. A spiking network model shows that recurrent inhibition can control this activity-state switch, and more broadly the gain of spiking responses to excitatory inputs. In biological CRH PVN neurons ex vivo, the injection of whole-cell currents derived from our computational model recreates the in vivo-like switch between RB and SS, providing direct evidence that physiologically relevant network inputs enable state-dependent computation in single neurons. Together, we present a novel mechanism for state-dependent activity dynamics in CRH PVN neurons. 

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3. 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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4. Magnetic Stimulation of Dissociated Cortical Neurons on a Planar Mulitelectrode Array

   Mukesh, S; Zeller-Townson, R; Butera, R; Bhatti, P (March 2019, International IEEE/EMBS Conference on Neural Engineering)

   We perform experiments to study the magnetic stimulus-induced changes in neural activity in dissociated cortical neurons with different stimulation parameters. The goal of performing these studies is to build on the results from our previous work that suggested magnetic stimulation may lead to improved performance of cochlear implants. A magnetic stimulator is assembled using a micro-scale coil. To detect small changes in activity, we use glass substrate MEAs to measure culture-wide synaptically-mediated response to stimulation, rather than the direct activation of individual neurons. Our initial findings show magnetic stimulation is associated with changes in network-wide firing rates, beyond those expected by spontaneous drift in activity. This suggests that the magnetic stimulation parameters we used were able to evoke neural activity. However, we observe substantial differences in the type of change induced in neural activity in different cultures and with different stimulation parameters, some showing increases in activity and others showing decreases in activity. This may be due to differences in the number and type of neurons (inhibitory or excitatory) activated by stimulation in different experiments, which in turn may be affected by differences in stimulator location and alignment, differences in stimulus pulse waveform and amplitudes, or differences in culture density or cell morphology. We also compare the power consumption and heating of this stimulation technique with that of electrical stimulation. Finally, a need to optimize the experimental setup to allow longer experiments is identified, to reach definite conclusions. 

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5. Detection of latent brain states from spontaneous neural activity in the amygdala

   https://doi.org/10.1371/journal.pcbi.1012247  

   Aucoin, Alexa; Lin, Kevin K; Gothard, Katalin M (February 2025, PLOS Computational Biology)

   Hennig, Matthias Helge (Ed.)

   The amygdala responds to a large variety of socially and emotionally salient environmental and interoceptive stimuli. The context in which these stimuli occur determines their social and emotional significance. In canonical neurophysiological studies, the fast-paced succession of stimuli and events induce phasic changes in neural activity. During inter-trial intervals, neural activity is expected to return to a stable and featureless level of spontaneous activity, often called baseline. In previous studies we found that context, such as the presence of a social partner, induces brain states that can transcend the fast-paced succession of stimuli and can be recovered from the spontaneous, inter-trial firing rate of neurons. Indeed, the spontaneous firing rates of neurons in the amygdala are different during blocks of gentle grooming touches delivered by a trusted social partner, and during blocks of non-social airflow stimuli delivered by a computer-controlled air valve. Here, we examine local field potentials (LFPs) recorded during periods of spontaneous activity to determine whether information about context can be extracted from these signals. We found that information about social vs. non-social context is present in the local field potential during periods of spontaneous activity between the application of grooming and airflow stimuli, as machine learning techniques can reliably decode context from spectrograms of spontaneous LFPs. No significant differences were detected between the nuclei of the amygdala that receive direct or indirect inputs from areas of the prefrontal cortex known to coordinate flexible, context-dependent behaviors. The lack of nuclear specificity suggests that context-related synaptic inputs arise from a shared source, possibly interoceptive inputs, that signal the physiological state of the body during social and non-social blocks of tactile stimulation. 

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