Changes In Firing Patterns Research Articles

Spatial Analysis, Interactive Visualisation and GIS-Based Dashboard for Monitoring Spatio-Temporal Changes of Hotspots of Bushfires over 100 Years in New South Wales, Australia

The 2019–2020 bushfire season is estimated to be one of the worst fire seasons on record in Australia, especially in New South Wales (NSW). The devastating fire season ignited a heated public debate on whether prescribed burning is an effective tool for preventing bushfires, and how the extent of bushfires has been changing over time. The objective of this study is to answer these questions, and more specifically to identify how bushfire patterns have changed in the last 100 years in NSW. To do so, we conducted a spatio-temporal analysis on prescribed burns and bushfires using a 100-year dataset of bushfires. More specifically, three research questions were developed, with each one of them addressed differently. First, generalised linear modelling was applied to assess the changes in fire patterns. Second, a correlation analysis was conducted to examine whether prescribed burns are an effective tool for reducing bushfire risk. Third, a spatio-temporal analysis was applied to the bushfire location data to explore spatio-temporal clusters of high and low values for bushfires, known as hotspots and coldspots, respectively. The study found that the frequency of bushfires has increased over time; however, it did not identify a significant trend of change in their size. Based on the results of this study for the relationship between prescribed burns and bushfires, it seems impossible to determine whether prescribed burns effectively reduce bushfire risk. Thus, further analysis with a larger amount of data is required in the future. The results of the spatio-temporal analysis showed that cold spots are propagated around metropolitan areas such as Sydney, while hotspots are concentrated in rural areas such as the North Coast and South Coast regions of NSW. The analysis found four statistical areas that have become new bushfire frequency hotspots in the 2019–2020 bushfire season. These areas combined have about 40,000 residents and at least 13,000 built dwellings. We suggest that further analysis is needed in the field to determine if there is a pattern of movement of bushfire towards metropolitan areas. To make the results of this research accessible to the public, an online interactive GIS-based dashboard was developed. The insight gained from the spatial and temporal analyses in this research is crucial to making smarter decisions on allocating resources and developing preventive or mitigating strategies.

In vivo patch-clamp recordings reveal distinct subthreshold signatures and threshold dynamics of midbrain dopamine neurons

The in vivo firing patterns of ventral midbrain dopamine neurons are controlled by afferent and intrinsic activity to generate sensory cue and prediction error signals that are essential for reward-based learning. Given the absence of in vivo intracellular recordings during the last three decades, the subthreshold membrane potential events that cause changes in dopamine neuron firing patterns remain unknown. To address this, we established in vivo whole-cell recordings and obtained over 100 spontaneously active, immunocytochemically-defined midbrain dopamine neurons in isoflurane-anaesthetized adult mice. We identified a repertoire of subthreshold membrane potential signatures associated with distinct in vivo firing patterns. Dopamine neuron activity in vivo deviated from single-spike pacemaking by phasic increases in firing rate via two qualitatively distinct biophysical mechanisms: 1) a prolonged hyperpolarization preceding rebound bursts, accompanied by a hyperpolarizing shift in action potential threshold; and 2) a transient depolarization leading to high-frequency plateau bursts, associated with a depolarizing shift in action potential threshold. Our findings define a mechanistic framework for the biophysical implementation of dopamine neuron firing patterns in the intact brain.

Frequency-dependent spike-pattern changes in motor cortex during thalamic deep brain stimulation.

The cerebellar-receiving area of the motor thalamus is the primary anatomical target for treating essential tremor with deep brain stimulation (DBS). Although neuroimaging studies have shown that higher stimulation frequencies in this target correlate with increased cortical metabolic activity, less is known about the cellular-level functional changes that occur in the primary motor cortex (M1) with thalamic stimulation and how these changes depend on the frequency of DBS. In this study, we used a preclinical animal model of DBS to collect single-unit spike recordings in M1 before, during, and after DBS targeting the cerebellar-receiving area of the motor thalamus (VPLo, nucleus ventralis posterior lateralis pars oralis). The effects of VPLo-DBS on M1 spike rates, interspike interval entropy, and peristimulus phase-locking were compared across stimulus pulse train frequencies ranging from 10 to 130 Hz. Although VPLo-DBS modulated the spike rates of 20-50% of individual M1 cells in a frequency-dependent manner, the population-level average spike rate only weakly depended on stimulation frequency. In contrast, the population-level entropy measure showed a pronounced decrease with high-frequency stimulation, caused by a subpopulation of cells that exhibited strong phase-locking and general spike-pattern regularization. Contrarily, low-frequency stimulation induced an entropy increase (spike-pattern disordering) in a relatively large portion of the recorded population, which diminished with higher stimulation frequencies. These results also suggest that changes in phase-locking and spike-pattern entropy are not necessarily equivalent pattern phenomena, but rather that they should both be weighed when quantifying stimulation-induced spike-pattern changes.NEW & NOTEWORTHY The network mechanisms of thalamic deep brain stimulation (DBS) are not well understood at the cellular level. This study investigated the neuronal firing rate and pattern changes in the motor cortex resulting from stimulation of the cerebellar-receiving area of the motor thalamus. We showed that there is a nonintuitive relationship between general entropy-based spike-pattern measures and phase-locked regularization to DBS.

Observed changes in fire patterns and possible drivers over Central Africa

Fire is an integral part of Earth’s system that links regional and global biogeochemical cycles, human activities, and ecosystems. Global estimates for biomass burning indicate that Africa is responsible for ~70% of global burned area and ~50% of fire-related carbon emissions. Previous studies have documented an overall decline in burned area in the African continent, but changes in fire patterns, such as the frequency and size of different fire categories, have not been assessed. In this study, long-term fire trends were investigated using the latest burned area data from the MODerate resolution Imaging Spectroradiometer (MODIS) and the Global Fire Emission Database (GFED4s) over Central Africa (10°E–40°E, 15°N–15°S). A 3D (latitude, longitude, time) connected-component labeling algorithm was applied to identify individual fires and their sizes. The results show a decline in burned area by 2.7–3.2 Mha yr−1 (~1.3% yr−1) for the period 2003–2017, particularly in northern Central Africa. This decline was attributed to significant decreases in both fire frequency and size, particularly for large fires (>100 ha) which contribute to ~90% of the total burned area. Burned area declined in tropical savannas and grasslands but increased at the edges of the Congolese rainforest. A random forest regression model was applied to quantify the influences of climatic conditions, fuel availability, and agricultural activity on burned area changes. Overall, suppressed fuel, increased dry season length, and decreased rainfall contributed to significant declines in burned area in savannas and grasslands. At the edges of the southern Congolese rainforest, suppressed rainfall and warmer temperature were responsible for the increased burned area.

Meteorological normalisation of PM10 using machine learning reveals distinct increases of nearby source emissions in the Australian mining town of Moranbah

The impacts of poor air quality on human health are becoming more apparent. Businesses and governments are implementing technologies and policies in order to improve air quality. Despite this the PM10 air quality in the mining town of Moranbah, Australia, has worsened since measurements commenced in 2011. The annual average PM10 concentrations during 2012, 2017, 2018 and 2019 have all exceeded the Australian National Environmental Protection Measure's standard, and there has been an increase in the frequency of exceedances of the daily standard. The average annual increase in PM10 was 1.2 ±0.5 μg m−3 per year between 2011 and 2019 and has been 2.5 ±1.2 μg m−3 per year since 2014. The cause of this has not previously been established. Here, two machine learning algorithms (gradient boosted regression and random forest) have been implemented to model and then meteorologically normalise PM10 mass concentrations measured in Moranbah. The best performing model, using the random forest algorithm, was able to explain 59% of the variance in PM10 using a range of meteorological, environmental and temporal variables as predictors. An increasing trend after normalising for these factors was found of 0.6 ± 0.5 μg m−3 per year since 2011 and 1.7 ± 0.3 μg m−3 per year since 2014. These results indicate that more than half of the increase in PM10 is due to a rise in local emissions in the region. The remainder of the rise in PM10 was found to be due to a decrease of soil water content in the surrounding region, which can facilitate higher dust emissions. Whether the presence of open-cut coal mines exacerbated the role of soil water content is unclear. Although fires can have drastic effects on the local air quality, changes in fire patterns are not responsible for the rising trend. PM10 composition measurements or more detailed data relating to local sources is still needed to better isolate these emissions. Nonetheless, this study highlights the need and potential for action by industry and government to improve the air quality and reduce health risks for the nearby population.

Shedding light on dyskinesias.

Dopamine replacement therapy with L-DOPA remains the most widely prescribed treatment for Parkinson disease. However, prolonged treatment due to disease progression frequently causes unwanted motor movements known as levodopa-induced dyskinesias. Previous studies have established that alterations to the efferent circuitry of the striatum, a principal component of the basal ganglia, are in part responsible for the pathological motor consequences of prolonged levodopa treatment. While the role of the striatal direct pathway is widely accepted, the engagement of the striatal indirect pathway in dyskinetic pathophysiology is still under consideration. However, recent investigations have finally shown that the activity of both striatal pathways changes as a consequence of dopamine depletion and dyskinetic behavioural conditions. In addition, it has been reported that drug-induced structural alterations to indirect pathway medium spiny neurons, together with associated changes in synaptic plasticity and firing patterns, could contribute importantly to the development of dyskinesia. These findings, together with recent opto- and chemogenetic studies, suggest that a critical imbalance in the activity between both striatal pathways is sufficient to cause dyskinesia in both rodent and primate models of Parkinson disease. In animal models, and in human patients, dyskinetic behaviours elicited by this efferent pathway imbalance can be achieved even in the absence of dopamine denervation. In this review, we summarize recent and past findings to better understand this complex pathology with the aim of pursuing specific cell-type therapies to re-balance efferent striatal activity.

Modulating electrophysiology of motor neural networks via optogenetic stimulation during neurogenesis and synaptogenesis

Control of electrical activity in neural circuits through network training is a grand challenge for biomedicine and engineering applications. Past efforts have not considered evoking long-term changes in firing patterns of in-vitro networks by introducing training regimens with respect to stages of neural development. Here, we used Channelrhodopsin-2 (ChR2) transfected mouse embryonic stem cell (mESC) derived motor neurons to explore short and long-term programming of neural networks by using optical stimulation implemented during neurogenesis and synaptogenesis. Not only did we see a subsequent increase of neurite extensions and synaptophysin clustering, but by using electrophysiological recording with micro electrode arrays (MEA) we also observed changes in signal frequency spectra, increase of network synchrony, coordinated firing of actions potentials, and enhanced evoked response to stimulation during network formation. Our results demonstrate that optogenetic stimulation during neural differentiation can result in permanent changes that extended to the genetic expression of neurons as demonstrated by RNA Sequencing. To our knowledge, this is the first time that a correlation between training regimens during neurogenesis and synaptogenesis and the resulting plastic responses has been shown in-vitro and traced back to changes in gene expression. This work demonstrates new approaches for training of neural circuits whose electrical activity can be modulated and enhanced, which could lead to improvements in neurodegenerative disease research and engineering of in-vitro multi-cellular living systems.

Activation Complexity: A Cognitive Impairment Tool for Characterizing Neuro-isolation

Electroencephalography (EEG) is a method for recording electrical activity, indicative of cortical brain activity from the scalp. EEG has been used to diagnose neurological diseases and to characterize impaired cognitive states. When the electrical activity of neurons are temporally synchronized, the likelihood to reach their threshold potential for the signal to propagate to the next neuron, increases. This phenomenon is typically analyzed as the spectral intensity increasing from the summation of these neurons firing. Non-linear analysis methods (e.g., entropy) have been explored to characterize neuronal firings, but only analyze temporal information and not the frequency spectrum. By examining temporal and spectral entropic relationships simultaneously, we can better characterize how neurons are isolated, (the signal’s inability to propagate to adjacent neurons), an indicator of impairment. A novel time-frequency entropic analysis method, referred to as Activation Complexity (AC), was designed to quantify these dynamics from key EEG frequency bands. The data was collected during a cognitive impairment study at NASA Langley Research Center, involving hypoxia induction in 49 human test subjects. AC demonstrated significant changes in EEG firing patterns characterize within explanatory (p < 0.05) and predictive models (10% increase in accuracy). The proposed work sets the methodological foundation for quantifying neuronal isolation and introduces new potential technique to understand human cognitive impairment for a range of neurological diseases and insults.

Lévy noise-induced near-death spikes and phase transitions of a biological neural network

Near-death spikes or near-death surges are a sudden increase in neuron activity in the human brain before neurons end their firings. Just before a person is clinically dead, such spikes are observed in certain cases, so the name is near-death spikes. The reason for this behavior is the lack of oxygen in brain (Chawla et al. in J Palliat Med 12(12):1095–1100, 2009). In this study, it is demonstrated that a particular type of noise called Levy noise can generate such activity in the neural network of the worm Caenorhabditis elegans. The study identified different parameter regions of noise at which the network makes transitions from one synchronous state to another and the mechanism behind them. Such transitions are already reported in cortical regions of brain (Canavero et al. in Surg Neurol Int 7(Suppl 24):S623–S625, 2016). During the transition period between asynchronous and synchronous firing states, network is more susceptible to changes in firing pattern of individual neurons (Zandt et al. in PLoS ONE 6(7):e22127, 2011; Uzuntarla et al. Neural Netw 110:131–140, 2019). In this work, it is demonstrated that the recognized parameter regions can be used to control the network dynamics. The study also identified Levy noise values at which the network displays generation of waves of different frequencies. This result suggests a new method for neurostimulation in the case of traumatic brain injury. The study reveals that the characteristic exponent ($$\alpha $$) of the noise has better influence on the network dynamics than the scale parameter of noise (D) and the synaptic coupling constant (Gsyn) of the network. The neuronal network even displayed Gamma oscillations for large values of $$\alpha $$. If the parameters of the neurons are made chaotic, the network firing rate is diminished and it displayed Delta and Theta oscillations.

Impact of higher order network structure on emergent cortical activity.

Synaptic connectivity between neocortical neurons is highly structured. The network structure of synaptic connectivity includes first-order properties that can be described by pairwise statistics, such as strengths of connections between different neuron types and distance-dependent connectivity, and higher order properties, such as an abundance of cliques of all-to-all connected neurons. The relative impact of first- and higher order structure on emergent cortical network activity is unknown. Here, we compare network structure and emergent activity in two neocortical microcircuit models with different synaptic connectivity. Both models have a similar first-order structure, but only one model includes higher order structure arising from morphological diversity within neuronal types. We find that such morphological diversity leads to more heterogeneous degree distributions, increases the number of cliques, and contributes to a small-world topology. The increase in higher order network structure is accompanied by more nuanced changes in neuronal firing patterns, such as an increased dependence of pairwise correlations on the positions of neurons in cliques. Our study shows that circuit models with very similar first-order structure of synaptic connectivity can have a drastically different higher order network structure, and suggests that the higher order structure imposed by morphological diversity within neuronal types has an impact on emergent cortical activity.

Individual Differences in Amphetamine Locomotor Sensitization are Accompanied with Changes in Dopamine Release and Firing Pattern in the Dorsolateral Striatum of Rats

Not all the people that consume drugs of abuse develop addiction. In this sense, just a percentage of rats express locomotor sensitization after repeated psychostimulant exposure. Neurochemical evidence has shown that locomotor sensitization is associated with changes in dorsolateral striatum (DLS) activity. However, it is unknown if individual differences observed in locomotor sensitization are related to differential neuro-adaptations in DLS activity. In this study, we measured basal dopamine (DA) levels and single unit activity in the DLS of anesthetized rats, after repeated amphetamine (AMPH) administration. Rats were treated with AMPH 1.0 mg/kg ip or saline ip for 5 days. Following 5 days of withdrawal, a challenge dose of AMPH 1.0 mg/kg ip was injected. In-vivo microdialysis experiments and single unit recording were carried out twenty-four hours after the last AMPH injection. Sensitized rats showed increased basal DA levels and baseline firing rate of medium spiny neurons (MSNs) compared to non-sensitized rats. The local variation index (Lv) was used to measure the firing pattern of MSNs. In saline rats, a bursty firing pattern was observed in MSNs. A decrease in MSNs baseline Lv accompanies the expression of AMPH locomotor sensitization. Moreover, a decrease in Lv after an acute AMPH 1.0 mg/kg injection was only observed in saline and sensitized rats. Our results show individual differences in DLS basal DA levels and firing pattern after repeated AMPH administration, suggesting that an hyperfunction of nigrostriatal pathway, accompanied by a decrease in DLS MSNs firing irregularity underlies the expression of AMPH locomotor sensitization.

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).

Modulation of Neural and Muscular Adaptation Processes During Resistance Training by Fish Protein Ingestions in Older Adults.

Assessments of both neural and muscular adaptations during interventions would provide valuable information for developing countermeasures to age-related muscle dysfunctions. We investigated the effect of fish protein ingestion on training-induced neural and muscular adaptations in older adults. Twenty older adults participated 8 weeks of isometric knee extension training intervention. The participants were divided into two groups who took fish protein (n = 10, Alaska pollack protein, APP) or casein (n = 10, CAS). Maximal muscle strength during knee extension, lower extremity muscle mass (body impedance method), and motor unit firing pattern of knee extensor muscle (high-density surface electromyography) were measured before, during, and after the intervention. Muscle strength were significantly increased in both CAS (124.7 ± 5.8%) and APP (117.1 ± 4.4%) after intervention (p < .05), but no significant differences between the groups were observed (p > .05). Significant increases in lower extremity muscle mass from 0 to 8 weeks were demonstrated only for APP (102.0 ± 3.2, p < .05). Greater changes in motor unit firing pattern following intervention were represented in CAS more than in APP. These results suggest that nutritional supplementations could modulate neural and muscular adaptations following resistance training and fish protein ingestion preferentially induces muscular adaptation without the detectable neural adaptation in older adults.

Acute L-DOPA administration reverses changes in firing pattern and low frequency oscillatory activity in the entopeduncular nucleus from long term L-DOPA treated 6-OHDA-lesioned rats

The pathophysiology of Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID) is associated with aberrant neuronal activity and abnormal high levels of oscillatory activity and synchronization in several basal ganglia nuclei and the cortex. Previously, we have shown that the firing activity of neurons in the substantia nigra pars reticulata (SNr) is relevant in dyskinesia and may be driven by subthalamic nucleus (STN) hyperactivity. Conversely, low frequency oscillatory activity and synchronization in these structures seem to be more important in PD because they are not influenced by prolonged L-DOPA administration. The aim of the present study was to assess (through single-unit extracellular recording techniques under urethane anaesthesia) the neuronal activity of the entopeduncular nucleus (EPN) and its relationship with LID and STN hyperactivity, together with the oscillatory activity and synchronization between these nuclei and the cerebral cortex in 6-OHDA-lesioned rats that received long term L-DOPA treatment (or not). Twenty-four hours after the last L-DOPA injection the firing activity of EPN neurons in long term L-DOPA treated 6-OHDA-lesioned rats was more irregular and bursting compared to sham rats, being those alterations partially reversed by the acute challenge of L-DOPA. No correlation between EPN neurons firing activity and abnormal involuntary movements score was found. However, there was a significant correlation between the firing activity parameters of EPN and STN neurons recorded from long term L-DOPA treated 6-OHDA-lesioned rats. Low frequency oscillatory activity and synchronization both within the EPN and with the cerebral cortex were enhanced in 6-OHDA-lesioned animals. These changes were reversed by the acute L-DOPA challenge only in long term L-DOPA treated 6-OHDA-lesioned rats. Altogether, these results obtained from long term L-DOPA treated 6-OHDA-lesioned rats suggest (1) a likely relationship between STN and EPN firing patterns and spiking phases induced by changes after prolonged L-DOPA administration and (2) that the effect of L-DOPA on the firing pattern, low frequency oscillatory activity and synchronization in the EPN may have a relevant role in LID.

Evaluating the efficacy of cannabidiol to manage surgically induced neuropathic pain in a preclinical rat model: Are T cells a sexually dimorphic target?

ABSTRACTBackground: Considering the poorly understood etiology and complex symptoms of chronic neuropathic pain (NP), the lack of effective treatments, and sex-dependent differences in the neuroimmune system as well as in antinociceptive responses to existing pharmacological agents, the potential to therapeutically target the endocannabinoid system as a means of treating this type of intractable pain is clinically relevant and timely. Chronic NP may involve the utilization of distinct immune cell populations in males and females that differentially affect supraspinal and spinal neuromodulation. It is therefore important to investigate the effects of cannabidiol (CBD) on chronic NP-induced nociceptive responses in both sexes.Aims: Evaluating whether the expression of markers associated with CD4+ T cells are affected by CBD in a sexually dimorphic manner will provide key insights into the contribution of these adaptive immune cells to the onset and progression of NP.Methods: Future research will be directed toward examining the potential sex-dependent effects of this nonpsychotropic cannabinoid relative to vehicle in a preclinical model of chronic postsurgical NP. Specifically, (1) differences in nociceptive behavior, (2) chronic changes in neural firing patterns, and (3) up- or downregulation of markers associated with CD4+ T cells in relevant tissues will be evaluated to better understand CBD-mediated neuroimmune modulatory effects in males and females.Conclusions: Chronic postsurgical pain is a growing clinical problem. Current treatment strategies rely on opioid-based therapeutics, which affect patient quality of life and are associated with addiction and withdrawal. Treatment of nerve injuries with CBD could provide an effective alternative to manage NP. Understanding its mechanisms of action will provide important insights into the sex-dependent application of this nonpsychoactive cannabinoid, setting the groundwork for large-scale Canadian clinical trials in women and men presenting with chronic pain.

Cholinergic Transmission at Muscarinic Synapses in the Striatum Is Driven Equally by Cortical and Thalamic Inputs

SUMMARYThe release of acetylcholine from cholinergic interneurons (ChIs) directly modulates striatal output via muscarinic receptors on medium spiny neurons (MSNs). While thalamic inputs provide strong excitatory input to ChIs, cortical inputs primarily regulate MSN firing. Here, we found that, while thalamic inputs do drive ChI firing, a subset of ChIs responds robustly to stimulation of cortical inputs as well. To examine how input-evoked changes in ChI firing patterns drive acetylcholine release at cholinergic synapses onto MSNs, muscarinic M4-receptor-mediated synaptic events were measured in MSNs overexpressing G-protein gated potassium channels (GlRK2). Stimulation of both cortical and thalamic inputs was sufficient to equally drive muscarinic synaptic events in MSNs, resulting from the broad synaptic innervation of the stimulus-activated ChI population across many MSNs. Taken together, this indicates an underappreciated role for the extensive cholinergic network, in which small populations of ChIs can drive substantial changes in post-synaptic receptor activity across the striatum.

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.

Cav3.2 T‐type calcium channel mutation influences kindling‐induced thalamic neuronal firing patterns in Genetic Absence Epilepsy Rats From Strasbourg

Recent data indicate that amygdala kindling leads to significant changes in interictal neuronal firing patterns of thalamic reticular nucleus (TRN) neurons by decreasing the spontaneous firing rate and increasing burst firing in nonepileptic control (NEC) rats. Genetic Absence Epilepsy Rats From Strasbourg (GAERS) were resistant to these kindling-induced firing changes in TRN neurons, and are also resistant to the progression of kindling. We investigated whether a homozygous, missense, single nucleotide mutation (R1584P) in the Cav 3.2 T-type Ca2+ channel gene, which has been correlated with the expression of absence seizures in GAERS, influenced kindling progression and TRN firing patterns. Double-crossed (GAERS vs NEC; F2) rats that were homozygous for the Cav 3.2 mutation (PP) and those negative for the mutation (RR) were implanted with a stimulating electrode in the amygdala. Rats received a total of 30 kindling stimulations at their afterdischarge threshold current twice daily, and kindling progression was evaluated. Thereafter, the extracellular neuronal activity of TRN neurons was recorded in vivo under neuroleptanesthesia to investigate the influence of Cav 3.2 mutation on TRN firing patterns. We found that the R1584P mutation did not affect kindling progression in F2 crosses (P= 0.78). However, it influenced kindling-induced neuronal firing of TRN neurons. After 30 stimulations, RR rats exhibited a lower firing rate and a higher percentage of burst firing compared to PP rats. The decrease in firing frequency was correlated with the increase in the amount of burst firing in RR rats (R2 =0.497). Our findings suggest that mutation in Cav 3.2 T-type Ca2+ channels may play a role in the resistance to kindling-induced changes in TRN neurons to a low-frequency and high-percentage bursting pattern seen in association with the convulsive stages of amygdala kindling, but is not in itself enough to explain the resistance to kindling progression observed in GAERS.

Changes in auditory thalamus neural firing patterns after acoustic trauma in rats

Tinnitus is an abnormal phantom perception associated with cochlear trauma, and is thought to cause changes in the rates and patterns of firing neurons in the central auditory pathway. Recent studies have suggested a key role for the auditory thalamus, the medial geniculate nucleus (MGN), in the generation of tinnitus as it may serve a gating function for information en route to cortex. Dysfunctional gating would lead to abnormal activity reaching cortex and hence inappropriate perception, tinnitus, would occur. In this study we compared spontaneous MGN firing rates and burst firing parameters in Wistar rats with and without behavioural evidence of tinnitus following an acoustic trauma. Data were also compared with animals subjected to sham surgery and at an early time-point (2 weeks) after acoustic trauma. Acoustic trauma resulted in a temporary but not a permanent threshold loss and no differences were found in spontaneous firing rate between any of the groups. However, acoustic trauma, whether resulting in tinnitus or not, was accompanied by a significant decrease in the percentage of neurons showing burst firing. In bursting neurons, the number of spikes occurring in a burst and the number of burst per minutes was also significantly reduced compared to the sham group. Our results show that in our rat model without permanent threshold loss, elevated spontaneous firing rates are not associated with acoustic trauma and/or tinnitus and that burst firing parameters are associated with acoustic trauma but are not a neural signature for tinnitus.

Abrupt Change in Electrophysiological Properties Begins From Postnatal Day 7 Before Hearing Onset in the Developing Mice Auditory Cortical Layer II/III Neurons.

ObjectivesIn the developing auditory cortex, maturation of electrophysiological properties and cell types before and after hearing onset has been reported previously. However, the exact timing of firing pattern change has not been reported. In this study, firing pattern change was investigated from postnatal day 3 (P3) to P12 in auditory cortical layer II/III neurons to investigate whether firing pattern changes dramatically after a specific point during development.MethodsICR mice pups aged from P3 to P12 were sacrificed to obtain 300-mm-thick brain slices containing the primary auditory cortex. From cortical layer II/III neurons, the patterns of action potential firing generated by current injection were examined using whole cell current clamp technique and the characteristics of Na+ currents involved in action potential firing were investigated using whole cell voltage clamp technique.ResultsFrom P3 to P6, most cells did not show action potential firing (29 of 46 cells), and some cells responding to current injection showed a single action potential at the initial depolarizing current step (17 of 46 cells). This firing pattern changes from P7. From P7 to P9, cells begin to show regular spiking to current injection. The spiking frequency increased after P10. In studying Na+ current with whole cell voltage clamp, Na+ current densities increased gradually (32.0±2.0 pA/pF [P3–P6, n=7], 51.2±2.0 pA/pF [P7–P9, n=13], and 69.5±3.7 pA/pF [P10–P12, n=13]) in low external [Na+] condition. Na+ current recovery was accelerated and inactivation curves shifted to hyperpolarization with age.ConclusionAs regular spiking cells were observed from P7 but never from P3 to P6, P7 might be regarded as an important milestone in the development of auditory cortical layer II/III neurons. This change might mainly result from the increase in Na+ current density.