Increase In Firing Frequency Research Articles

Age-related increase in the excitability of mouse layer V pyramidal neurons in the primary motor cortex is accompanied by an increased persistent inward current.

Sarcopenia, or pathological age-related loss of muscle strength and mass, contributes to physical function impairment in older adults. While current understanding of sarcopenia is centered mostly on neuromuscular mechanisms, mounting evidence supports that deficits at the level of the primary motor cortex (PMC) play a significant role. Despite the importance of the PMC to initiate movement, understanding of how age affects the excitability of layer V pyramidal neurons (LVPNs) of the PMC is limited. To address this, we used the whole-cell patch clamp technique to measure the excitability of LVPNs of the PMC in young, late adulthood, and old mice. Old LVPNs had increased firing frequency and membrane input resistance, but no differences in action potential kinetics versus young and late adulthood mice. Since changes in the persistent inward current (PIC) are known to contribute to changes in motor neuron excitability, we measured LVPN PICs as a putative contributor to LVPN excitability. The PIC amplitude was increased in old LVPN via increases in Na+ and Ca2+ PICs, in addition to being active across a wider voltage range. Given that LVPN function is integral to initiation of voluntary muscle contraction, altered LVPN excitability likely contributes to age-related impairment of physical function.

S-(+)-mecamylamine increases the firing rate of serotonin neurons and diminishes depressive-like behaviors in an animal model of stress

Mecamylamine, a noncompetitive blocker of nicotinic acetylcholine receptors (nAChRs), is the racemic mixture of two stereoisomers: S-(+)-mecamylamine (S-mec) and R-(−)-mecamylamine (R-mec), with distinct interactions with α4β2 nAChRs. It has been shown that mecamylamine increases glutamate release and excites serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). In this study, we separately evaluated the effects of S-mec and R-mec on 5-HT neuron excitability. S-mec (3 μM) increased firing frequency by 40 %, while R-mec (3 μM) raised it by only 22 %. S-mec acts as a positive allosteric modulator on high-sensitivity (HS) α4β2 nAChRs at glutamate terminals, enhancing spontaneous excitatory postsynaptic currents (sEPSCs) in 5-HT neurons. Conversely, R-mec decreased sEPSCs by blocking HS α4β2 nAChRs and reduced GABA-mediated inhibitory currents (sIPSCs) by blocking α7 nAChRs at GABAergic terminals. These mechanisms make S-mec more effective than R-mec in enhancing 5-HT neuron firing. Moreover, combining S-mec with TC-2559, a selective agonist of HS α4β2 nAChRs, increased firing frequency by 65 %, exceeding the effect of S-mec alone. To validate these findings, we evaluated the antidepressant effects of S-mec (1 mg/kg) combined with TC-2559 or RJR-2403, another α4β2 nAChR agonist. This combination successfully reduced depression-like behaviors, suggesting a potential treatment strategy for patients resistant to conventional antidepressants.

Changes in D4 and GABAA subunit α3 receptors in the thalamic reticular nucleus caused by unilateral lesion of the globus pallidus.

The thalamic reticular nucleus controls information processing in thalamocortical neurons. GABAergic neurons present in this nucleus express the α3 subunit of post‑synaptic GABAA receptors, which bind GABA from globus pallidus neurons. Pallidal neurons, in turn, have dopaminergic D4 receptors in their axon terminals. The thalamic reticular nucleus connects reciprocally with the thalamus, and it receives afferents from the brain cortex, as well as from other brain structures that have an important role in the modulation of the thalamic network. Based on the above, the purpose of this study was to assess the electrophysiological and molecular effects of unilateral lesion of the globus pallidus on the electric activity of the thalamic reticular nucleus. Two‑month‑old male rats were used. The right globus pallidus was lesioned with quinolinic acid. Seven days after the lesion, ipsilateral turning was registered, confirming the lesion. Afterward, electrophysiological evaluation of the right thalamic reticular nucleus' electrical activity was performed. Subsequently, mRNA expression for D4 receptors and subunit α3, as well as protein content were assessed in the right reticular nucleus. Pallidum lesion caused an increase in firing frequency and decreased firing bursts of reticular neurons. In addition, dopaminergic D4 mRNA, as well as protein increased. In contrast, GABAergic GABAA subunit α3 expression was suppressed, but protein content increased. These results show that the globus pallidus regulates firing in reticular neurons through D4 receptors and subunit α3 of GABAA receptor in the reticular nucleus of the thalamus.

Abstract 53: Chronic Angiotensin-(1-7) Treatment May Enhance GABAergic Neurotransmission onto Melanocortin-4 Receptor Neurons in The Hypothalamic Paraventricular Nucleus in a Sex-Specific Manner

Angiotensin (Ang)-(1-7) is a protective hormone of the renin-angiotensin system that lowers blood pressure in animal models of cardiovascular disease; however, the precise mechanisms remain incompletely understood. Recent data from our laboratory suggests that blood pressure lowering effects of Ang-(1-7) may involve the arcuate nucleus of the hypothalamus (ARC). We have shown that Ang-(1-7) activates proopiomelanocortin (POMC)-containing neurons in the ARC. While ARC POMC neuron activation canonically increases blood pressure by stimulating melanocortin-4 receptors (MC4R) in the hypothalamic paraventricular nucleus (PVN), these neurons also release the inhibitory neurotransmitter GABA. Selective activation of these GABAergic POMC neurons could serve as a novel mechanism to lower blood pressure. In this study, we hypothesized that Ang-(1-7) treatment inhibits PVN MC4R neuron activity via enhanced GABAergic function. To test this, male and female MC4R-GFP mice were implanted with osmotic mini pumps at 14 weeks of age and treated chronically with either Ang-(1-7) (400 ng/kg/min) or saline. After six weeks of drug administration, action potential firing of PVN MC4R-expressing neurons was examined using cell attached electrophysiology. To assess GABAergic function, changes in action potential firing frequency following bath application of the GABA A receptor antagonist bicuculline (10 μm) were compared between Ang-(1-7) and saline treated animals (n=4-6 mice/group). While Ang-(1-7) did not alter baseline firing frequency of MC4R PVN neurons in male mice (1.5±0.6 vs. 1.1±0.3 Hz saline; p=0.630, unpaired t-test), it enhanced bicuculline responsiveness as indicated by a greater peak increase in action potential firing frequency (156.9±18.0 vs. 106.2±6.8 % saline; p=0.013). In female mice, Ang-(1-7) increased baseline action potential firing frequency of PVN MC4R neurons (1.5±0.4 vs. 0.3±0.1 Hz saline; p=0.026) but did not alter bicuculline responsiveness (111.0±5.3 vs. 143.2±25.3 % saline; p=0.241). Overall, our data suggest that Ang-(1-7) enhances GABAergic neurotransmission onto PVN MC4R neurons in a sex-specific manner. These data provide new insight into the neural mechanisms of Ang-(1-7), which could have implications for understanding the beneficial cardiovascular effects of this hormone. Additional studies are needed to examine this inhibitory neurocircuit in the context of hypertension as well as precise mechanisms underlying the observed sex differences.

Effects of Wildfires on Soil Organic Carbon in Boreal Permafrost Regions: A Review

ABSTRACTWildfire strongly influences permafrost environment and soil organic carbon (SOC) pool. In this study, we reviewed the effects of fire severity, time after a fire, and frequency on SOC in boreal permafrost regions. This review highlighted several key points: the effect of wildfires on SOC increased with an increase of fire severity, and the amount of vegetation returned and surface organic matter replenished was less in a short term, which resulted in a significantly lower SOC content compared to that of before the fire. Within a short period after fire, the SOC in near‐surface permafrost and the active layer decreased significantly due to the loss of above ground biomass, permafrost thaw, and increased microbial decomposition; as the years pass after a fire, the SOC gradually accumulates due to the contributions of litter layer accumulation and rooting systems from different stages of succession. The increase in fire frequency accelerated permafrost thawing and the formation of thermokarst, resulting in the rapid release of a large amount of soil carbon and reduced SOC storage. Therefore, the study on the effects of wildfires on SOC in the boreal permafrost region is of great significance to understanding and quantifying the carbon balance of the ecosystem.

Cholinergic stimulation stabilizes TRPM4 in the plasma membrane of cortical pyramidal neurons.

TRPM4 is a calcium activated non-selective cation channel, impermeable to Ca2+, in neurons it has been implicated in the regulation of the excitability and in the persistent firing. Cholinergic stimulation is also implicated in changes in excitability that leads neurons to an increased firing frequency, however it is not clear whether TRPM4 is involved in the cholinergic-induced increase in firing frequency. Here using a combination of patch clamp electrophysiology, Ca2+ imaging, immunofluorescence, fluorescence recovery after photobleaching (FRAP) and pharmacological approach, we demonstrate that carbachol (Cch) increases firing frequency, intracellular Ca2+ and that TRPM4 inhibition using 9-Ph and CBA reduces firing frequency and decreases the peak in intracellular Ca2+ induced by Cch in cortical pyramidal neurons in culture. Moreover, we determined that cholinergic stimulation reduces TRPM4 recycling and stabilizes TRPM4 in the plasma membrane. Together our results indicate that cholinergic stimulation increases firing in a TRPM4 dependent manner, and also increases the TRPM4 stability in the membrane, suggesting that TRPM4 is locked in microdomains in the membrane, possibly signaling or cytoskeleton proteins complexes.

The Dynamics of Fire Activity in the Brazilian Pantanal: A Log-Gaussian Cox Process-Based Structural Decomposition

We present a novel statistical methodology for analyzing shifts in spatio-temporal fire occurrence patterns within the Brazilian Pantanal, utilizing remote sensing data. Our approach employs a Log-Gaussian Cox Process to model the spatiotemporal dynamics of fire occurrence, deconstructing the intensity function into components of trend, seasonality, cycle, covariates, and time-varying spatial effects components. The results indicate a negative correlation between rainfall and fire intensity, with lower precipitation associated with heightened fire intensity. Forest formations exhibit a positive effect on fire intensity, whereas agricultural land use shows no significant impact. Savannas and grasslands, typical fire-dependent ecosystems, demonstrate a positive relationship with fire intensity. Human-induced fires, often used for agricultural purposes, contribute to an increase in both fire frequency and intensity, particularly in grassland areas. Trend analysis reveals fluctuating fire activity over time, with notable peaks in 2018–2021.

Low power nanoscale S-FED based single ended sense amplifier applied in integrate and fire neuron circuit

Current advancements in neuromorphic computing systems are focused on decreasing power consumption and enriching computational functions. Correspondingly, state-of-the-art system-on-chip developers are encouraged to design nanoscale devices with minimum power dissipation and high-speed operation. This paper deals with designing a sense amplifier based on side-contacted field-effect diodes to reduce the power-delay product (PDP) and the noise susceptibility, as critical factors in neuron circuits. Our findings reveal that both static and dynamic power consumption of the S-FED-based sense amplifier, equal to 1.86 μW and 1.92 fW/GHz, are × 243.03 and × 332.83 lower than those of the conventional CMOS counterpart, respectively. While the sense-amplifier circuit based on CMOS technology undergoes an output voltage deviation of 170.97 mV, the proposed S-FED-based one enjoys a minor output deviation of 27.31 mV. Meanwhile, the superior HIGH-level and LOW-level noise margins of the S-FED-based sense amplifier to the CMOS counterparts (∆NMH = 70 mV and ∆NML = 120 mV), respectively, can ensure the system-level operation stability of the former one. Subsequent to the attainment of an area-efficient, low-power, and high-speed S-FED-based sense amplifier (PDP = 187.75 × 10–18 W s) as a fundamental building block, devising an innovative integrate-and-fire neuron circuit based on S-FED paves the way to realize a new generation of neuromorphic architectures. To shed light on this context, an S-FED-based integrate-and-fire neuron circuit is designed and analyzed utilizing a sense amplifier and feedback loop to enhance spiking voltage and subsequent noise immunity in addition to an about fourfold increase in firing frequency compared to CMOS-based ones.

Seventy-five years of vegetation change after fire in Tasmanian alpine heathland

Context Alpine ecosystems are threatened by warming and an associated increase in fire frequency. There is a gap in our knowledge of succession in Tasmanian alpine heath more than 50 years after fire. The literature suggests that the alpine successional progression usually involves decreasing rates of change, decreasing differences among fire ages, ongoing transitions among shrub species, ongoing transitions from some lifeforms/species to others, and that warming results in increases in species richness. Aims We test for these tendencies up to 75 years from fire in alpine vegetation on kunanyi/Mount Wellington, Tasmania, Australia. Methods We documented the changes in vegetation structure and composition between 1998 and 2022 in plots on either side of an alpine fire boundary in the alpine heathland and used earlier data and observations to extend the record of change after fire to 75 years. We put these changes in the context of the only area of alpine vegetation that was not burnt in 1947 or later. Key results The area last burnt in 1947 exhibited declines in all lifeform covers between 1998 and 2022. All lifeforms except tall shrubs and mat shrubs declined in cover in the area last burnt in 1962. By 2022, shrub cover in the 1962-burnt area had not attained equivalence with the area last burnt in 1947. Herbs had the most dramatic decline in both fire-age classes. There were few shrub seedlings in 2022. All but six taxa, three being exotic, were observed in both the plots and previous broader surveys. Increases in species richness caused by the upward migration of lower-elevation species were not observed. The long-unburnt patch lacked the major dominant of the 1947-burnt plots, namely Orites acicularis, and was dominated by a gymnosperm absent from most of the mountain. Conclusions Succession follows the initial floristic composition model. The differences in trajectories from the 1947 and 1962 fires could possibly be due to desiccation or abrasion damage from increasing wind speeds and temperatures. There are strong indications of further potential change in the absence of fire. Implications The slow rate of recovery and its on-going nature emphasise the importance of keeping fire out of this vegetation type.

Decreased GABAergic Neurotransmission Promotes Breathing Upon Emergence From Hibernation

The respiratory network must produce reliable output for an animal to survive. Although respiratory motor plasticity is well appreciated, how plasticity mechanisms work to promote robustness following environmental perturbations that disrupt breathing is less clear. During underwater hibernation, respiratory neurons of bullfrogs remain inactive for months, triggering a suite of compensatory mechanisms that aim to maintain respiratory function. We hypothesized that GABAergic inhibition would decrease following hibernation. In control animals, respiratory frequency was under control of GABAAR signaling. Specifically, block of GABAARs dose-dependently decreased respiratory burst frequency in the in vitro brainstem preparation (n=5 preparations). After hibernation, GABAA receptor block had little to no impact on respiratory burst frequency, suggesting the network was no longer reliant on GABAergic inhibition to maintain normal frequency (n=5 preparations). The loss of inhibition was specific to the respiratory network because non-respiratory motor activity and large seizure-like bursts were similarly triggered by GABAA receptor blockade in intact brainstem preparations from controls and hibernators. We next used a semi-intact preparation that maintains functional respiratory-synaptic input onto rhythmic motor neurons to identify compensatory changes in GABAergic tone at the level of the motor neuron. In controls, the firing rate of respiratory motoneurons was constrained by a phasic GABAAR tone because focal application of bicuculline, a GABAAR antagonist, led to an increase in phasic firing frequency (n=12 cells). After hibernation, this bicuculline-mediated increase in phasic firing frequency was attenuated suggesting phasic inhibition onto the motor neuron had decreased (n=9 cells). Brain slice recordings of identified vagal motor neurons revealed that postsynaptic GABAA receptor strength was unchanged following hibernation (n=16 control cells; n=16 hibernation cells). Taken together, our results suggest that GABAergic activity is decreased in premotor networks following hibernation. Despite this dramatic loss of GABAergic function, respiratory output from control preparations was indistinguishable from hibernators. To elucidate the functional impacts of loss of GABAergic activity, we tested the network’s ability to produce output at colder temperatures. In controls, respiratory output slowed as temperature decreased, with most networks nearly silent at 8 degrees Celsius (n=5 preparations). Interestingly, in controls low dose block of GABAA receptors promoted respiratory activity at cold temperatures, with frequency not statistically different than baseline at any temperature tested (n=4 preparations). This suggests that the loss of premotor GABAergic activity we observed could work to promote motor output at colder temperatures, which works adaptively for the animal when emerging from hibernation. NIH R01NS114514 (JS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Mechanisms Underlying Long-Term Facilitation in the Carotid Body

Glutamate and γ-aminobutyric acid (GABA) are major modulators of excitatory and inhibitory transmission in the mammalian brain. Glutamate transmission is critical for neural plasticity, learning and memory, whereas GABA plays a fundamental role in regulating neuronal excitability and facilitating the generation of neural oscillations. Our data indicates that both glutamate and GABA are released in the carotid body (CB) to modulates its response to hypoxia. Objectives: We set out to investigate whether repeated stimulation with glutamate and GABA induces lasting effects on CB afferent discharge. Hypothesis: We hypothesised that glutamate/GABA mediates long-term facilitation (LTF) of CB afferent activity. Methods: We mined high-throughput RNA sequence data and used immunohistochemistry to map components underlying neuroplasticity in the CB in Wistar and Spontaneously-hypertensive rats (SHR). CSN discharge was measured as a functional readout of CB function from an ex vivo arterially perfused carotid artery-CB preparation. Data: We catalogue the expression of glutamate receptors (R) and transporters in the rat and mouse CB. We found N-methyl-D-aspartic acid receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR) and transporters to be localised to the CB chemosensory cells. Targeted administration of 15 mM glutamate activated the carotid sinus nerve ( p=0.003). Repetitive [5 times, 2-minute duration, 5-minute intervals] application of 15 mM glutamate evoked LTF of CB afferent discharge as demonstrated by both a 12-fold increase in basal firing frequency (0.78 ± 0.37 vs 1232 ± 596 spikes 1s−1; p = 0.004) over 60 minutes ( p = 0.004) and amplification of the evoked response to chemical hypoxia (CN−; 1.23 μmol bolus) by 2-fold ( p = 0.009). The stimulation paradigm was specific as neither application of glutamate, 5 times for 1-minute at 5-minute intervals, nor a single glutamate exposure evoked LTF. In contrast, repeated application of 15mM GABA [3 times for 1-minute at 5-minute intervals] evoked long-term depression (LTD) of CB afferent activity as seen by a reduced basal discharge from 10.5 to 3.5 spikes 1s−1 ( p = 0.0004) and a 2-fold suppression of the response to chemical hypoxia ( p = 3.71 x 10−5). Summary of the data: Repetitive exposure to glutamate using a specific protocol increased basal discharge of CB afferent output akin to LTF and caused sensitisation of evoked responses to CN−. Repeated exposures of GABA depressed the CB basal discharge akin to LTD. A statement of the conclusions: It is conceivable that processes such as LTP and LTD operate in the CB to modulate the set point of peripheral chemoreceptor sensitivity and its state-dependent tonicity; the role of LTP in peripheral chemoreflex sensitisation in disease remains to be determined. Research was supported by the Health Research Council of New Zealand and the Sidney Taylor Trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

WNK1 is a central osmolality sensor for arginine vasopressin release and acts through the OSR1/SPAK kinase cascade

Background: Maintaining internal osmolality constancy and water homeostasis is essential for life. The circumventricular organs (CVOs) of the brain, including the organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO), lack a blood-brain barrier. Neurons in OVLT and SFO detect increases in serum osmolality that stimulate the production of vasopressin (AVP) in paraventricular nuclei (PVN) to be released in the posterior pituitary. We have recently reported that WNK1 in sensory neurons in CVOs functions as an osmolality sensor for AVP release (Jin et al., JCI, 2023). WNK1 activates Kv3.1 to increase action potential, traveling down to PVN to increase AVP synthesis for release from the posterior pituitary. Here, we propose that OSR1/SPAK acts as the downstream kinase for WNK1 in regulating AVP release. We further investigated the regulation of vasopressin release by the WNK1-OSR1/SPAK cascade in response to extracellular hyperosmolality. Methods: Cre recombinase-carrying retrograde AAV virus was stereotaxically injected into PVN nuclei from normal mice and SPAK-null mice with a homozygous OSR1-floxed allele (SAPK−/−;OSR1flox/flox). Metabolic cage studies were performed on mice. Urine output, water intake, serum osmolality, serum AVP, and copeptin levels were measured. K+ currents were measured from the OVLT neurons by whole-cell patch clamp. Results: Increased osmolality, either by water restriction or mannitol injection, activated OSR1/SPAK in OVLT, as evident by increased serine-373 phospho-SPAK and serine-325 phospho-OSR. Like the WNK1 deletion, the double deletion of OSR/SPAK in OVLT caused polyuria with decreased urine osmolality that persisted in water restriction. Circulating levels of AVP and copeptin were increased by water restriction in control mice. In contrast, water restriction failed to increase the levels in OSR/SPAK-deletion mice. Knockdown of the Kv3.1 channel in OVLT by shRNA showed the central diabetes insipidus (DI) phenotype as well. Hypertonicity increased K+ currents and WNKs inhibitor prevented the increase in OVLT neurons. Conclusions: Mice with neuronal-specific OSR1/SPAK deletion have water homeostasis defects consistent with partial central DI; Evidence supporting that OSR1/SPAK acts downstream of WNK1 to regulate AVP release; WNK1-OSR1/SPAK activates Kv3.1 to increase firing frequency of neurons projecting from CVOs to PVN. Our findings reveal that an intracellular protein acts as a sensor for extracellular tonicity and provide fresh insights into the mechanisms by which the body maintains osmolality constancy. Future studies will investigate how OSR1/SPAK regulates Kv3.1 channels. NIDDK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Shifting fire regimes cause continent-wide transformation of threatened species habitat.

Human actions are causing widespread increases in fire size, frequency, and severity in diverse ecosystems globally. This alteration of fire regimes is considered a threat to numerous animal species, but empirical evidence of how fire regimes are shifting within both threatened species' ranges and protected areas is scarce, particularly at large spatial and temporal scales. We used a big data approach to quantify multidecadal changes in fire regimes in southern Australia from 1980 to 2021, spanning 415 reserves (21.5 million ha) and 129 threatened species' ranges including birds, mammals, reptiles, invertebrates, and frogs. Most reserves and threatened species' ranges within the region have experienced declines in unburnt vegetation (≥30 y without fire), increases in recently burnt vegetation (≤5 y since fire), and increases in fire frequency. The mean percentage of unburnt vegetation within reserves declined from 61 to 36% (1980 to 2021), whereas the mean percentage of recently burnt vegetation increased from 20 to 35%, and mean fire frequency increased by 32%, with the latter two trends primarily driven by the record-breaking 2019 to 2020 fire season. The strongest changes occurred for high-elevation threatened species, and reserves of high elevation, high productivity, and strong rainfall decline, particularly in the southeast of the continent. Our results provide evidence for the widely held but poorly tested assumption that threatened species are experiencing widespread declines in unburnt habitat and increases in fire frequency. This underscores the imperative for developing management strategies that conserve fire-threatened species in an increasingly fiery future.

Short-Interval, High-Severity Wildfire Depletes Diversity of Both Extant Vegetation and Soil Seed Banks in Fire-Tolerant Eucalypt Forests

Many plant species are well-adapted to historical fire regimes. An increase in the severity, frequency, and extent of wildfires could compromise the regenerative capacity of species, resulting in permanent shifts in plant diversity. We surveyed extant vegetation and soil seed banks across two forest types with contrasting historical fire regimes—Shrubby Dry Forest (fire return interval: 10–20 years) and Sub-Alpine Woodland (50–100 years). Over the past 20 years, both forests have been subject to repeated, high-severity wildfires at intervals significantly shorter than their historical return intervals. We examined the soil seed bank response to fire-cued germination, and whether the plant diversity in soil seed banks and extant vegetation demonstrated similar responses to short-interval, high-severity wildfires. The soil seed bank demonstrated a positive response to heat in combination with smoke, and for the Sub-Alpine Woodland, this was limited to sites more frequently burnt by fire. With an increase in fire frequency, there was a decline in species richness and Shannon’s Diversity and a shift in species composition in both extant vegetation and the soil seed bank. The fire frequency effects on the relative richness of trait associations were restricted to the Shrubby Dry Forest, and included an increase in short-lived obligate seeders, wind-dispersed species, and ant-dispersed shrubs in burnt relative to long unburnt sites in both extant vegetation and the soil seed bank. Graminoids were the most abundant component of the soil seed banks of Sub-Alpine Woodlands, and this increased with more frequent fire, with a similar trend (p = 0.06) in extant vegetation. Clear shifts in plant diversity in both soil seed banks and extant vegetation in forest types with contrasting historical fire regimes suggest that emerging fire regimes are pushing ecosystems beyond their historical range of variability, including potentially more flammable states and a decline in the buffering capacity of soil seed banks.

Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia.

Vincristine-induced peripheral neuropathy is a common side effect of vincristine treatment, which is accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced pain are not well understood. We have established an animal model to investigate pathophysiological mechanisms of vincristine-induced pain. Our previous studies have shown that the tetrodotoxin-sensitive voltage-gated sodium channel Nav1.6 in medium-diameter dorsal root ganglion (DRG) neurons contributes to the maintenance of vincristine-induced allodynia. In this study, we investigated the effects of vincristine administration on excitability in small-diameter DRG neurons and whether the tetrodotoxin-resistant (TTX-R) Nav1.8 channels contribute to mechanical allodynia. Current-clamp recordings demonstrated that small DRG neurons become hyper-excitable following vincristine treatment, with both reduced current threshold and increased firing frequency. Using voltage-clamp recordings in small DRG neurons, we now show an increase in TTX-R current density and a -7.3 mV hyperpolarizing shift in the half-maximal potential (V1/2) of activation of Nav1.8 channels in vincristine-treated animals, which likely contributes to the hyperexcitability that we observed in these neurons. Notably, vincristine treatment did not enhance excitability of small DRG neurons from Nav1.8 knockout mice, and the development of mechanical allodynia was delayed but not abrogated in these mice. Together, our data suggest that sodium channel Nav1.8 in small DRG neurons contributes to the development of vincristine-induced mechanical allodynia.

Long-term post-fire recovery of oribatid mites depends on the recovery of soil properties in a fire-adapted pine forest

Fire is a highly important factor affecting the forest structure as well as its functions. The understanding of the post-fire recovery mechanisms could be especially useful in the face of globally increasing fire frequencies. Fire-adapted forests in Minnesota provide a unique opportunity to study these recovery mechanisms due to their long and well-documented history of prescribed burnings and wildfires. We investigated oribatid mite (Acari: Oribatida) assemblages along a 126-year post-fire chronosequence, together with soil physical, chemical and microbial properties (e.g. bulk density, organic matter content, C, N and P content, microbial biomass). Whereas the effect of prescribed burning was negligible, the wildfire decreased oribatid density (–86 %) and diversity (–38 %) for at least 13 years. The recovery of oribatid mites corresponded to the changes in soil properties, being correlated negatively to bulk density and positively to organic matter content, water holding capacity and microbial activity and biomass. The recovery did not depend simply on the time elapsed since fire, but it was rather a complex response to long-term (15–20 years), fire-induced changes in the soil environment.

Fire effects on pollination and plant reproduction: a quantitative review.

Fire may favour plant flowering by opening the vegetation and increasing abiotic resource availability. Increased floral display size can attract more pollinators and increase the absolute fruit and seed production immediately after the fire. However, anthropogenic increases in fire frequency may alter these responses. We aim to assess the effects of fire on pollination and reproductive success of plants at the global scale. We performed a systematic literature review and meta-analyses to examine overall fire effects as well as different fire parameters on pollination and on plant reproduction. We also explored to what extent the responses vary among pollinators, pollination vectors, plant regeneration strategies, compatibility systems, vegetation types and biomes. Most studies were conducted in fire-prone ecosystems. Overall, single fires increased pollination and plant reproduction but this effect was overridden by recurrent fires. Floral visitation rates of pollinators were enhanced immediately following a wildfire, and especially in bee-pollinated plants. Fire increased the absolute production of fruits or seeds but not the fruit or seed set. The reproductive benefits were mostly observed in wind-pollinated (graminoids), herbaceous and resprouter species. Finally, fire effects on pollination were positively correlated with fire effects on plant reproductive success. Fire has a central role in pollination and plant sexual reproduction in fire-prone ecosystems. The increase in the absolute production of fruits and seeds suggests that fire benefits on plant reproduction are likely driven by increased abiotic resources and the consequent floral display size. However, reproduction efficiency, as measured by fruit or seed set, does not increase with fire. In contrast, when assessed on the same plant simultaneously, fire effects on pollination are translated into reproduction. Increased fire frequency due to anthropogenic changes can alter the nature of the response to fire.

Molecular mechanism responsible for sex differences in electrical activity of mouse pancreatic β cells.

In humans, type 2 diabetes mellitus shows a higher prevalence in men compared with women, a phenotype that has been attributed to a lower peripheral insulin sensitivity in men. Whether sex-specific differences in pancreatic β cell function also contribute is largely unknown. Here, we characterized the electrophysiological properties of β cells in intact male and female mouse islets. Elevation of glucose concentration above 5 mM triggered an electrical activity with a similar glucose dependence in β cells of both sexes. However, female β cells had a more depolarized membrane potential and increased firing frequency compared with males. The higher membrane depolarization in female β cells was caused by approximately 50% smaller Kv2.1 K+ currents compared with males but otherwise unchanged KATP, large-conductance and small-conductance Ca2+-activated K+ channels, and background TASK1/TALK1 K+ current densities. In female β cells, the higher depolarization caused a membrane potential-dependent inactivation of the voltage-gated Ca2+ channels (CaV), resulting in reduced Ca2+ entry. Nevertheless, this reduced Ca2+ influx was offset by a higher action potential firing frequency. Because exocytosis of insulin granules does not show a sex-specific difference, we conclude that the higher electrical activity promotes insulin release in females, improving glucose tolerance.

Forest fires in the Indian Central Himalaya: major drivers, implications, and mitigation measures

ABSTRACT Forest fires pose a significant threat in the Central Himalaya due to both natural and human factors. This study investigates key drivers, consequences, and mitigation measures. Data on 2022 forest fire incidents, affected areas, and economic losses were collected from the State Forest Department, Dehradun, and analyzed using statistical methods. The 2022 forest fire areas were mapped using data from the USGS and NASA FIRMS portals, revealing highly sensitive zones in river valleys and mid-altitudes below 1800 m, covering 13% of the total forest area (approximately 40,000 ha). These regions primarily host monsoon deciduous and flammable pine forests. Recent years have witnessed a notable increase in fire frequency and intensity, attributed to warming river valleys, middle altitudes, and dry climate spells during the fire season. This pioneering study recommends risk reduction strategies, including managing dry pine leaves, forest replacement, constructing fire lines, and providing fire control training to rural communities. Adopting these measures can effectively mitigate the escalating threat of forest fires in the Central Himalaya.

Wildfires in the Larch Range within Permafrost, Siberia

Throughout the larch range, warming leads to frequent fires and an increase in burned areas. We test the hypothesis that fires are an essential natural factor that reset larch regeneration and support the existence of larch forests. The study area included Larix sibirica and L. gmelinii ranges within the permafrost zone. We used satellite-derived and field data, dendrochronology, and climate variables analysis. We found that warming led to an increase in fire frequency and intensity, mean, and extreme (>10,000 ha) burned areas. The burned area is increasing in the northward direction, while fire frequency is decreasing. The fire rate exponentially increases with decreasing soil moisture and increasing air temperature and air drought. We found a contrasting effect of wildfire on regeneration within continuous permafrost and within the southern lowland boundary of the larch range. In the first case, burnt areas regenerated via abounded larch seedlings (up to 500,000+ per ha), whereas the south burns regenerated mostly via broadleaf species or turned into grass communities. After the fire, vegetation GPP was restored to pre-fire levels within 3–15 years, which may indicate that larch forests continue to serve as carbon stock. At the southern edge of the larch range, an amplified fire rate led to the transformation of larch forests into grass and shrub communities. We suggested that the thawing of continuous permafrost would lead to shrinking larch-dominance in the south. Data obtained indicated that recurrent fires are a prerequisite for larch forests’ successful regeneration and resilience within continuous permafrost. It is therefore not necessary to suppress all fires within the zone of larch dominance. Instead, we must focus fire suppression on areas of high natural, social, and economic importance, permitting fires to burn in vast, larch-dominant permafrost landscapes.