Changes In Firing Rate Research Articles

Biomechanical Stresses Due to Tissue Micromotion at the Neural Interface Modulate Intracellular Membrane Potentials

Micromotion in brain tissue at a neural interface can arise from respiration and vascular pulsation besides behavioral perturbations. We have reported 2-4 µm of brain tissue displacements in rodents due to vascular pulsation and 10-30 µm due to respiration. It has been hypothesized that the periodic membrane potential (MP) changes observed in neuronal intracellular recordings correlated to tissue micromotion were an artifact. In this study, using penetrating microelectrodes for intracellular recordings in an Aplysia californica abdominal ganglion, we show that the membrane potentials and firing rates change due to periodic cell compression. We show that these membrane potential changes are modulated by calcium, potassium, and mechanosensitive channel blockers. There were no membrane potential changes in response to periodic stresses <1.5 kPa in n=5 cells. Increases in amplitude of periodic stresses resulted in a linear increase in MP fluctuations; action potentials were generated in response to stresses >3 kPa for n=2 silent neurons suggesting the role of mechanosensitive receptors. Neurons that were already firing changed their firing rate in n=3 cells indicating that MP fluctuations are physiological and not artifacts. Application of 5-HT to the ganglion cell, resulted in decreased firing rate indicating that MP fluctuations are potentially modulated by mechanosensitive SK-channels in Aplysia. Preliminary in vivo rodent experiments show that periodic, intracellular membrane potentials fluctuate in the order of 10-30 mV. Using a custom double barrel pipette to (1) record neural activity and (2) to deliver drugs locally, these periodic membrane potential changes due to breathing and heart rate are inhibited by the mechanosensitive ion channel blocker gadolinium chloride. Results of this study suggest that cells at the electrode-brain tissue interface could be potentially undergoing chronic sub-threshold neuromodulation that could impact its long-term functionality and viability.

Continuous Representations of Speed by Striatal Medium Spiny Neurons.

The striatum is critical for controlling motor output. However, it remains unclear how striatal output neurons encode and facilitate movement. A prominent theory suggests that striatal units encode movements in bursts of activity near specific events, such as the start or end of actions. These bursts are theorized to gate or permit specific motor actions, thereby encoding and facilitating complex sequences of actions. An alternative theory has suggested that striatal neurons encode continuous changes in sensory or motor information with graded changes in firing rate. Supporting this theory, many striatal neurons exhibit such graded changes without bursting near specific actions. Here, we evaluated these two theories in the same recordings of mice (both male and female). We recorded single-unit and multiunit activity from the dorsomedial striatum of mice as they spontaneously explored an arena. We observed both types of encoding, although continuous encoding was more prevalent than bursting near movement initiation or termination. The majority of recorded units did not exhibit positive linear relationships with speed but instead exhibited nonlinear relationships that peaked at a range of locomotor speeds. Bulk calcium recordings of identified direct and indirect pathway neurons revealed similar speed tuning profiles, indicating that the heterogeneity in response profiles was not due to this genetic distinction. We conclude that continuous encoding of speed is a central component of movement encoding in the striatum.SIGNIFICANCE STATEMENT The striatum is a structure that is linked to volitional movements and is a primary site of pathology in movement disorders. It remains unclear how striatal neurons encode motor parameters and use them to facilitate movement. Here, we evaluated two models for this: a "discrete encoding model" in which striatal neurons facilitate movements with brief burst of activity near the start and end of movements, and a "continuous encoding model," in which striatal neurons encode the sensory or motor state of the animal with continuous changes in firing. We found evidence primarily in support of the continuous encoding model. This may have implications for understanding the striatal control of movement, as well as informing therapeutic approaches for treating movement disorders.

Effects of choice on neuronal activity in anterior cingulate, prelimbic, and infralimbic cortices in the rat: Comparison of serial lever pressing with delayed nonmatching to position.

The ability to choose between response alternatives based on their likely consequences depends on distributed neural circuits that involve rodent medial prefrontal cortex (mPFC). To understand the effects of choice on mPFC function, we compared the activity of mPFC neurons in rats performing two tasks: dynamic delayed nonmatching to position (dDNMTP), a task with a prefrontal-dependent conditional choice, and serial lever pressing (SLP), a task lacking a choice but trained in the same apparatus with sequences of actions and reinforcements matched to dDNMTP. More neurons exhibited event-related responses during dDNMTP than SLP. Average firing rate during recording sessions was higher during dDNMTP for neurons with event-related responses, but lower for neurons with activity unrelated to behavioural events. Thus, compared to SLP, dDNMTP appears to enhance the activity of neurons that represent behaviourally relevant information and to suppress the activity of neurons that do not. dDNMTP was associated with responses related to preparation and memory delay that were not observed during SLP as well as enhanced responses related to movement and reinforcement. These results provide evidence that choice in the dDNMTP task is associated with adaptive changes in background firing rates and coding properties of mPFC neurons.

Neurophysiological coding of space and time in the hippocampus, entorhinal cortex, and retrosplenial cortex.

Neurophysiological recordings in behaving rodents demonstrate neuronal response properties that may code space and time for episodic memory and goal-directed behaviour. Here, we review recordings from hippocampus, entorhinal cortex, and retrosplenial cortex to address the problem of how neurons encode multiple overlapping spatiotemporal trajectories and disambiguate these for accurate memory-guided behaviour. The solution could involve neurons in the entorhinal cortex and hippocampus that show mixed selectivity, coding both time and location. Some grid cells and place cells that code space also respond selectively as time cells, allowing differentiation of time intervals when a rat runs in the same location during a delay period. Cells in these regions also develop new representations that differentially code the context of prior or future behaviour allowing disambiguation of overlapping trajectories. Spiking activity is also modulated by running speed and head direction, supporting the coding of episodic memory not as a series of snapshots but as a trajectory that can also be distinguished on the basis of speed and direction. Recent data also address the mechanisms by which sensory input could distinguish different spatial locations. Changes in firing rate reflect running speed on long but not short time intervals, and few cells code movement direction, arguing against path integration for coding location. Instead, new evidence for neural coding of environmental boundaries in egocentric coordinates fits with a modelling framework in which egocentric coding of barriers combined with head direction generates distinct allocentric coding of location. The egocentric input can be used both for coding the location of spatiotemporal trajectories and for retrieving specific viewpoints of the environment. Overall, these different patterns of neural activity can be used for encoding and disambiguation of prior episodic spatiotemporal trajectories or for planning of future goal-directed spatiotemporal trajectories.

Ovarian Androgens Maintain High GnRH Neuron Firing Rate in Adult Prenatally-Androgenized Female Mice.

Changes in gonadotropin-releasing hormone (GnRH) release frequency from the brain help drive reproductive cycles. In polycystic ovary syndrome (PCOS), persistent high GnRH/luteinizing hormone (LH) frequency disrupts cycles and exacerbates hyperandrogenemia. Adult prenatally-androgenized (PNA) mice exhibit increased GnRH neuron firing rate, elevated ovarian androgens, and disrupted cycles, but before puberty, GnRH neuron activity is reduced in PNA mice compared with controls. We hypothesized that ovarian feedback mediates the age-dependent change in GnRH neuron firing rate in PNA vs control mice. Extracellular recordings of green fluorescent protein (GFP)-identified GnRH neurons were made 5 to 7 days after sham-surgery, ovariectomy (OVX), or, in adults, after OVX plus replacement of sub-male androgen levels with dihydrotestosterone implants (OVX + DHT). In 3-week-old mice, OVX did not affect GnRH neuron firing rate in either group. In adult controls, OVX increased GnRH neuron firing rate, which was further enhanced by DHT. In adult PNA mice, however, OVX decreased GnRH neuron firing rate, and DHT restored firing rate to sham-operated levels. In contrast to the differential effects of ovarian feedback on GnRH neuron firing rate, serum LH increased after OVX in both control and PNA mice and was not altered by DHT. Pituitary gene expression largely reflected changes expected with OVX, although in PNA but not control mice, DHT treatment increased Lhb expression. These results suggest prenatal androgen exposure programs marked changes in GnRH neuron regulation by homeostatic steroid feedback. PNA lowers GnRH neuron activity in low-steroid states (before puberty, OVX), and renders activity in adulthood dependent upon ongoing exposure to elevated ovarian androgens.

A Spike Train Distance Robust to Firing Rate Changes Based on the Earth Mover's Distance.

Neural spike train analysis methods are mainly used for understanding the temporal aspects of neural information processing. One approach is to measure the dissimilarity between the spike trains of a pair of neurons, often referred to as the spike train distance. The spike train distance has been often used to classify neuronal units with similar temporal patterns. Several methods to compute spike train distance have been developed so far. Intuitively, a desirable distance should be the shortest length between two objects. The Earth Mover’s Distance (EMD) can compute spike train distance by measuring the shortest length between two spike trains via shifting a fraction of spikes from one spike train to another. The EMD could accurately measure spike timing differences, temporal similarity, and spikes time synchrony. It is also robust to firing rate changes. Victor and Purpura (1996) distance measures the minimum cost between two spike trains. Although it also measures the shortest path between spike trains, its output can vary with the time-scale parameter. In contrast, the EMD measures distance in a unique way by calculating the genuine shortest length between spike trains. The EMD also outperforms other existing spike train distance methods in measuring various aspects of the temporal characteristics of spike trains and in robustness to firing rate changes. The EMD can effectively measure the shortest length between spike trains without being considerably affected by the overall firing rate difference between them. Hence, it is suitable for pure temporal coding exclusively, which is a predominant premise underlying the present study.

Thermoacoustic combustion instability of propane‐oxy‐combustion with CO2dilution: Experimental analysis

In this study, the effect of CO2 dilution on the thermoacoustic stability of propane-oxyfuel flames is studied in a non-premixed, swirl-stabilized combustor. The results, obtained at a fixed combustor power density (4 MW/m3 bar) and global stoichiometric equivalence ratio (Φ = 1.0), show that the oxy-flame is stable at 0% and low CO2 concentrations in the oxidizer. A self-amplifying coupling between heat release and pressure fluctuations was observed to occur at the CO2 concentration of 45%, which matches the point of flame transition from a jet-like to a V-shaped flame resulting from the formation of inner recirculation zone. The observed frequency for both the pressure and heat release oscillations is 465 Hz and the ensuing thermoacoustic instability is believed to have been resulted from vortexes and flame interactions. Subsequent to the coupling of the oscillations at the CO2 concentration of 45%, their amplitudes grew at 50% to 60% CO2 dilution levels. The maximum amplitude was observed at 60% CO2 concentration after which, as CO2 dilution level increases, the acoustic amplitude and that of its counterpart in the heat release spectrum decreased due to damping (energy dissipation) arising from heat loss and viscous dissipation. An increase in hydrogen concentration in the fuel and a decrease in the combustor power density were observed to lower the acoustic amplitude. Furthermore, a frequency shift is observed with a change in the combustor firing rate, which shows that the mode scales with the flow velocity, and therefore, unlikely to be a natural acoustic mode of the combustor. This study, therefore, reveals thermoacoustic instability in non-premixed oxy-combustion driven by changes in flame dynamics and macrostructures as the CO2 concentration in the oxidizer mixture varies.

Shaw and Shal voltage-gated potassium channels mediate circadian changes in Drosophila clock neuron excitability.

As in mammals, Drosophila circadian clock neurons display rhythms of activity with higher action potential firing rates and more positive resting membrane potentials during the day. This rhythmic excitability has been widely observed but, critically, its regulation remains unresolved. We have characterized and modelled the changes underlying these electrical activity rhythms in the lateral ventral clock neurons (LNvs). We show that currents mediated by the voltage-gated potassium channels Shaw (Kv3) and Shal (Kv4) oscillate in a circadian manner. Disruption of these channels, by expression of dominant negative (DN) subunits, leads to changes in circadian locomotor activity and shortens lifespan. LNv whole-cell recordings then show that changes in Shaw and Shal currents drive changes in action potential firing rate and that these rhythms are abolished when the circadian molecular clock is stopped. A whole-cell biophysical model using Hodgkin-Huxley equations can recapitulate these changes in electrical activity. Based on this model and by using dynamic clamp to manipulate clock neurons directly, we can rescue the pharmacological block of Shaw and Shal, restore the firing rhythm, and thus demonstrate the critical importance of Shaw and Shal. Together, these findings point to a key role for Shaw and Shal in controlling circadian firing of clock neurons and show that changes in clock neuron currents can account for this. Moreover, with dynamic clamp we can switch the LNvs between morning-like and evening-like states of electrical activity. We conclude that changes in Shaw and Shal underlie the daily oscillation in LNv firing rate.

Presynaptic dysregulation of the paraventricular thalamic nucleus causes depression-like behavior

The paraventricular thalamic nucleus (PVT) is a part of epithalamus and sends outputs to emotion-related brain areas such as the medial prefrontal cortex, nucleus accumbens, and amygdala. Various functional roles of the PVT in emotion-related behaviors are drawing attention. Here, we investigated the effect of manipulation of PVT neurons on the firing patterns of medial prefrontal cortical (mPFC) neurons and depression-like behavior. Extracellular single-unit recordings revealed that acute activation of PVT neurons by hM3Dq, an activation type of designer receptors exclusively activated by designer drugs (DREADDs), and administration of clozapine N-oxide (CNO) caused firing rate changes in mPFC neurons. Moreover, chronic presynaptic inhibition in PVT neurons by tetanus toxin (TeTX) increased the proportion of interneurons among firing neurons in mPFC and shortened the immobility time in the forced swimming test, whereas long-term activation of PVT neurons by hM3Dq caused recurrent hypoactivity episodes. These findings suggest that PVT neurons regulate the excitation/inhibition balance in the mPFC and mood stability.

Postpartum changes in affect-related behavior and VTA dopamine neuron activity in rats

The onset of motherhood is accompanied by alterations in emotional and affective behaviors. Many new mothers experience transient and mild depressive symptoms that typically resolve spontaneously (i.e. postpartum blues) but increase the risk for postpartum depression (PPD). There is little data regarding the neural adaptations occurring in response to parturition and shortly after birth that may be associated with these affective changes. Although the dopamine (DA) system is involved in affect, maternal motivation and PPD, little is known about postpartum DA function. We compared affective behavior in virgin and postpartum adult female rats at early and late time points. In vivo extracellular recordings of VTA DA neurons were performed to evaluate 3 parameters: number of active DA neurons (i.e. population activity), firing rate, and firing pattern. Compared with virgins, postpartum rats exhibited increased anxiety-like behavior in the elevated plus maze at 1-day postpartum; reduced social motivation at 1- and 3-days postpartum, reduced anxiety-like behavior in the novelty suppressed feeding test throughout the first week postpartum and increased forced swim test immobility at 1-day postpartum. 1- and 3-day postpartum females exhibited attenuated VTA population activity without changes in firing rate or pattern. None of these effects were observed in late postpartum females when compared with virgins. These data suggest that parturition induces time-dependent changes in a subset of affect-related behaviors and DA function during the postpartum period in rodents, with early postpartum females exhibiting depression-related phenotypes (i.e. low social motivation, higher immobility, blunted DA activity).

The asynchronous state's relation to large-scale potentials in cortex.

Understanding the relation between large-scale potentials (M/EEG) and their underlying neural activity can improve the precision of research and clinical diagnosis. Recent insights into cortical dynamics highlighted a state of strongly reduced spike count correlations, termed the asynchronous state (AS). The AS has received considerable attention from experimenters and theorists alike, regarding its implications for cortical dynamics and coding of information. However, how reconcilable are these vanishing correlations in the AS with large-scale potentials such as M/EEG observed in most experiments? Typically the latter are assumed to be based on underlying correlations in activity, in particular between subthreshold potentials. We survey the occurrence of the AS across brain states, regions, and layers and argue for a reconciliation of this seeming disparity: large-scale potentials are either observed, first, at transitions between cortical activity states, which entail transient changes in population firing rate, as well as during the AS, and, second, on the basis of sufficiently large, asynchronous populations that only need to exhibit weak correlations in activity. Cells with no or little spiking activity can contribute to large-scale potentials via their subthreshold currents, while they do not contribute to the estimation of spiking correlations, defining the AS. Furthermore, third, the AS occurs only within particular cortical regions and layers associated with the currently selected modality, allowing for correlations at other times and between other areas and layers.

Inflammation Induced Sensory Nerve Growth and Pain Hypersensitivity Requires the N-Type Calcium Channel Cav2.2.

Voltage-gated calcium channels (VGCCs) are important mediators of pain hypersensitivity during inflammatory states, but their role in sensory nerve growth remains underexplored. Here, we assess the role of the N-type calcium channel Cav2.2 in the complete Freund’s adjuvant (CFA) model of inflammatory pain. We demonstrate with in situ hybridization and immunoblotting, an increase in Cav2.2 expression after hind paw CFA injection in sensory neurons that respond to thermal stimuli, but not in two different mechanosensitive neuronal populations. Further, Cav2.2 upregulation post-CFA correlates with thermal but not mechanical hyperalgesia in behaving mice, and this hypersensitivity is blocked with a specific Cav2.2 inhibitor. Voltage clamp recordings reveal a significant increase in Cav2.2 currents post-CFA, while current clamp analyses demonstrate a significant increase in action potential frequency. Moreover, CFA-induced sensory nerve growth, which involves the extracellular signal-related kinase (ERK1/2) signaling pathway and likely contributes to inflammation-induced hyperalgesia, was blocked with the Cav2.2 inhibitor. Together, this work uncovers a role for Cav2.2 during inflammation, demonstrating that VGCC activity can promote thermal hyperalgesia through both changes in firing rates of sensory neurons as well as promotion of new neurite outgrowth.

Regulating firing rates in a neural circuit by activating memristive synapse with magnetic coupling

The change of firing rates depends on how synaptic features interact with intrinsic properties of cells in neural system. Considering the chemical synaptic features, we design a controllable memristive synapse with magnetic coupling that are voltage-controlled, nonlinear, and unidirectional. To explore the effect of firing rates on interactions between synapse and neuron, the memristive synaptic current involving excitation and inhibition is then mapped into a generalized neuronal model. We observe and characterize the appearance of counterintuitive behavior that increased excitatory memristive synaptic current leads to the decrease in firing rates, and increased inhibitory memristive synaptic current leads to the increase in firing rates in the neural circuit. For the counterintuitive phenomenon, we utilize a geometric dynamics method to provide an underlying dynamics mechanism how the excitatory or inhibitory current impacts the decrease or increase in firing rates.

The Concept of Transmission Coefficient Among Different Cerebellar Layers: A Computational Tool for Analyzing Motor Learning.

High-fidelity regulation of information transmission among cerebellar layers is mainly provided by synaptic plasticity. Therefore, determining the regulatory foundations of synaptic plasticity in the cerebellum and translating them to behavioral output are of great importance. To date, many experimental studies have been carried out in order to clarify the effect of synaptic defects, while targeting a specific signaling pathway in the cerebellar function. However, the contradictory results of these studies at the behavioral level further add to the ambiguity of the problem. Information transmission through firing rate changes in populations of interconnected neurons is one of the most widely accepted principles of neural coding. In this study, while considering the efficacy of synaptic interactions among the cerebellar layers, we propose a firing rate model to realize the concept of transmission coefficient. Thereafter, using a computational approach, we test the effect of different values of transmission coefficient on the gain adaptation of a cerebellar-dependent motor learning task. In conformity with the behavioral data, the proposed model can accurately predict that disruption in different forms of synaptic plasticity does not have the same effect on motor learning. Specifically, impairment in training mechanisms, like in the train-induced LTD in parallel fiber-Purkinje cell synapses, has a significant negative impact on all aspects of learning, including memory formation, transfer, and consolidation, although it does not disrupt basic motor performance. In this regard, the overinduction of parallel fiber-molecular layer interneuron LTP could not prevent motor learning impairment, despite its vital role in preserving the robustness of basic motor performance. In contrast, impairment in plasticity induced by interneurons and background activity of climbing fibers is partly compensable through overinduction of train-induced parallel fiber-Purkinje cell LTD. Additionally, blockade of climbing fiber signaling to the cerebellar cortex, referred to as olivary system lesion, shows the most destructive effect on both motor learning and basic motor performance. Overall, the obtained results from the proposed computational framework are used to provide a map from procedural motor memory formation in the cerebellum. Certainly, the generalization of this concept to other multi-layered networks of the brain requires more physiological and computational researches.

Temporal evolution of beta bursts in the parkinsonian cortical and basal ganglia network

Beta frequency oscillations (15 to 35 Hz) in cortical and basal ganglia circuits become abnormally synchronized in Parkinson's disease (PD). How excessive beta oscillations emerge in these circuits is unclear. We addressed this issue by defining the firing properties of basal ganglia neurons around the emergence of cortical beta bursts (β bursts), transient (50 to 350 ms) increases in the beta amplitude of cortical signals. In PD patients, the phase locking of background spiking activity in the subthalamic nucleus (STN) to frontal electroencephalograms preceded the onset and followed the temporal profile of cortical β bursts, with conditions of synchronization consistent within and across bursts. Neuronal ensemble recordings in multiple basal ganglia structures of parkinsonian rats revealed that these dynamics were recapitulated in STN, but also in external globus pallidus and striatum. The onset of consistent phase-locking conditions was preceded by abrupt phase slips between cortical and basal ganglia ensemble signals. Single-unit recordings demonstrated that ensemble-level properties of synchronization were not underlain by changes in firing rate but, rather, by the timing of action potentials in relation to cortical oscillation phase. Notably, the preferred angle of phase-locked action potential firing in each basal ganglia structure was shifted during burst initiation, then maintained stable phase relations during the burst. Subthalamic, pallidal, and striatal neurons engaged and disengaged with cortical β bursts to different extents and timings. The temporal evolution of cortical and basal ganglia synchronization is cell type-selective, which could be key for the generation/ maintenance of excessive beta oscillations in parkinsonism.

Stable Representations of Decision Variables for Flexible Behavior

Decisions occur in dynamic environments. In the framework of reinforcement learning, the probability of performing an action is influenced by decision variables. Discrepancies between predicted and obtained rewards (reward prediction errors) update these variables, but they are otherwise stable between decisions. Although reward prediction errors have been mapped to midbrain dopamine neurons, it is unclear how the brain represents decision variables themselves. We trained mice on a dynamic foraging task in which they chose between alternatives that delivered reward with changing probabilities. Neurons in the medial prefrontal cortex, including projections to the dorsomedial striatum, maintained persistent firing rate changes over long timescales. These changes stably represented relative action values (to bias choices) and total action values (to bias response times) with slow decay. In contrast, decision variables were weakly represented in the anterolateral motor cortex, a region necessary for generating choices. Thus, we define a stable neural mechanism to drive flexible behavior.

Context-Dependent Relationships between Locus Coeruleus Activation and Coordinated Neural Activity Patterns in the Anterior Cingulate Cortex

Ascending neuromodulatory projections from the locus coeruleus (LC) affect cortical neural networks via the release of norepinephrine (NE). However, the exact nature of these modulatory effects on neural activity patterns in vivo is not well understood. Here we show that in awake monkeys, LC activation is associated with changes in coordinated activity patterns in the anterior cingulate cortex (ACC). These effects, which are largely independent of changes in firing rates of individual ACC neurons, depend on the type of LC activation: ACC pairwise correlations are reduced when tonic (baseline) LC activity increases but are enhanced when external events drive phasic LC responses. Both effects also covary with pupil changes that reflect LC activation and arousal. These results suggest that modulations of information processing that reflect changes in coordinated activity patterns in cortical networks can, at least in part, result from ongoing, context-dependent, arousal-related changes in activation of the LC-NE system.

Modulation of Functional Connectivity Between Dopamine Neurons of the Rat Ventral Tegmental Area in vitro.

Micro Electrode Arrays were used to simultaneously record spontaneous extracellular action potentials from 10 to 30 dopamine neurons in acute brain slices from the lateral Ventral Tegmental Area (VTA) of the rat. The spike train of an individual neuron was used to characterize the firing pattern: firing rate, firing irregularity and oscillation frequency. Functional connectivity between a pair of neurons was quantified by the Paired Phase Consistency (PPC), taking the oscillation frequency as reference. Under baseline conditions the PPC was significantly different from zero and 42 of the 386 pairs of VTA neurons showed significant coupling. Fifty percent of the recorded dopamine neurons were part of the coupled VTA network. Raising extracellular potassium from 3.5 to 5 mM increased the mean firing rate of the dopamine neurons by 45%. The same increase could be induced by bath application of 300 μm glutamate. High potassium reduced the PPC, but it did not change during the glutamate application. Our findings imply that manipulating excitability has distinct and specific consequences for functional connectivity in the VTA network that cannot be directly predicted from the changes in neuronal firing rates. Functional connectivity reflects the spatial organization and synchronization of the VTA output and thus represents a unique element of the message that is sent to the mesolimbic projection area. It adds a dimension to pharmacological manipulation of the VTA micro circuit that might help to understand the pharmacological (side) effects of e.g., anti-psychotic drugs.

Prolonged post-stimulation response induced by 980-nm infrared neural stimulation in the rat primary motor cortex.

The post-stimulation response of neural activities plays an important role to evaluate the effectiveness and safety of neural modulation techniques. Previous studies have established the capability of infrared neural modulation (INM) on neural firing regulation in the central nervous system (CNS); however, the dynamic neural activity after the laser offset has not been well characterized yet. We applied 980-nm infrared diode laser light to irradiate the primary motor cortex of rats, and tungsten electrode was inserted to record the single-unit activity of neurons at the depth of 800-1000μm (layer V of primary motor cortex). The neural activities were assessed through the change of neural firing rate and firing pattern pre- and post-stimulation with various radiant exposures. The results showed that the 980-nm laser could modulate the firing properties of neurons in the deep layer of the cortex. More neurons with post-stimulation response (78% vs. 83%) were observed at higher stimulation intensity (0.803J/cm2 vs. 1.071J/cm2, respectively). The change of firing rate also increased with radiant exposures increasing, and the response lasted up to 4.5s at 1.071J/cm2, which was significantly longer than the theoretical thermal relaxation time. Moreover, the increasing Fano factors indicated the irregularity firing pattern of post-stimulation response. Our results confirmed that neural activity maintained a prolonged post-stimulation response after INM, which may provide necessary measurable data for optimization of INM applications in CNS.

Changing views of the pathophysiology of Parkinsonism.

Studies of the pathophysiology of parkinsonism (specifically akinesia and bradykinesia) have a long history and primarily model the consequences of dopamine loss in the basal ganglia on the function of the basal ganglia/thalamocortical circuit(s). Changes of firing rates of individual nodes within these circuits were originally considered central to parkinsonism. However, this view has now given way to the belief that changes in firing patterns within the basal ganglia and related nuclei are more important, including the emergence of burst discharges, greater synchrony of firing between neighboring neurons, oscillatory activity patterns, and the excessive coupling of oscillatory activities at different frequencies. Primarily focusing on studies obtained in nonhuman primates and human patients with Parkinson's disease, this review summarizes the current state of this field and highlights several emerging areas of research, including studies of the impact of the heterogeneity of external pallidal neurons on parkinsonism, the importance of extrastriatal dopamine loss, parkinsonism-associated synaptic and morphologic plasticity, and the potential role(s) of the cerebellum and brainstem in the motor dysfunction of Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.