The anterior cruciate ligament (ACL) is not merely a passive stabilizer of the knee, yet its injuries are still commonly treated as a mechanical problem despite growing evidence implicating the central nervous system (CNS). This mini review highlights the ACL as a critical sensory organ, housing mechanoreceptors that provide afferent feedback regarding the knee position. We further examine evidence across peripheral, cortical, and supraspinal levels to characterize CNS involvement in ACL injury.
Tonotopy is a hallmark feature of auditory structures that describes the spatial separation of sound frequencies along a gradient from high to low. Identifying biophysical differences along the frequency axis is essential for understanding how tonotopic maps develop in auditory structures and how these maps serve specific functions. In the mammalian cochlear nucleus and the analogous avian nucleus magnocellularis (NM), neurons are arranged along a tonotopic gradient resulting from ordered synaptic connections from the auditory nerve. While mature NM neurons exhibit some intrinsic (i.e., ion channel) differences along the tonotopic axis, it is unclear whether these intrinsic properties of high- and low-frequency neurons diverge in phenotype across development or if they instead converge by embryonic maturation to resemble each other, suggesting offset developmental timelines. Using whole-cell patch-clamp electrophysiology, we recorded from high- and low-frequency NM neurons in the embryonic chicken at early (E12-13), middle (E15-16), and late (E20-21) developmental stages. High- and low-frequency neurons differed in their action potential rise and repolarization rates during development, but these differences disappeared by late development, indicating a tonotopic developmental progression from high- to low-frequency neurons. However, neuronal input resistance, rheobase, and action potential latency were distinct across the tonotopic axis and remained so across development. High-frequency neurons had more low-voltage-activated potassium channels than low-frequency neurons at each developmental stage, thereby mediating differences in action potential properties. Overall, although some intrinsic properties converged in high- and low-frequency neurons by embryonic maturity, other disparities persisted, suggesting distinct phenotypes of high- and low-frequency neurons.
Interneurons in the motor cortex (M1) contribute to key motor functions, which are often altered after stroke. Changing the direction of transcranial magnetic stimulation (TMS) alters the onset time of motor evoked potentials (MEP). Yet, how stroke changes motor evoked potential (MEP) onset latency in association with directional TMS is not understood. The goals of the current study were to: 1) investigate directional MEP onset in the contralesional and ipsilesional hemispheres, and 2) characterize the relationship between MEP onset latency and motor function post-stroke. Twenty individuals with chronic stroke received single pulse, monophasic TMS over M1 in the lateral-medial (LM), posterior-anterior (PA), and anterior-posterior (AP) directions. Latency of activation of the corticospinal tract was indexed by subtracting MEP onset times from the paretic and non-paretic Extensor Carpi Radialis (ECR) muscle in the LM direction from the AP and PA directions in both hemispheres. Upper limb motor function in was quantified using the Wolf-Motor Function Test (WMFT). There was a significant difference between AP-LM and PA-LM MEP onset latencies within and between hemispheres. AP-LM MEP onset latency was longer in the contralesional as compared to the ipsilesional hemisphere. Hemispheric differences in AP-LM MEP onset latency explained a significant proportion of variance in WMFT performance between limbs. AP-LM MEP onset latency is post-stroke and larger hemispheric imbalances in AP-LM MEP onset times related to worse motor function. These data highlight a new relationship between connectivity of interneuron pools in the human motor cortex and motor function after stroke.
Vestibular contributions during walking are not uniform, but vary with gait phase, muscle group, and balance demands. Most previous experiments have focused on level-ground walking, with little known about how vestibular contributions change with terrain-imposed balance demands, such as slope. Our purpose was to quantify vestibular contributions during sloped walking. Participants walked on an instrumented treadmill at 1.0 m·s⁻¹ across five slopes (level, ±3°, ±6°), with and without stochastic electrical vestibular stimulation (EVS). To assess stability and gait adaptation, we measured step rate, length, width, and their variability from force plates. To probe vestibular contributions, we assessed time-frequency coherence between EVS and both whole-body responses, measured via mediolateral ground reaction forces, and lower-limb muscle responses, measured using electromyography. We found that whole-body coherence increased during incline but, unexpectedly, decreased during decline. Coherence for more proximal muscles, acting at the hip, mirrored whole body responses—increasing during incline and decreasing during decline, particularly during mid-to-late swing. More distal muscles acting at the ankle showed lower coherence across all slopes. This may reflect a balance strategy during incline walking that upregulates the vestibular system to guide limb trajectory throughout swing, rather than rely on active ankle control during stance, and a strategy during decline walking that downregulates the vestibular system and reduces balance demands through gait adaptations, such as shortened steps. Our findings highlight that vestibular contributions may be modulated in unexpected ways, reflecting not only the balance demands created by the terrain, but also the adaptive strategies adopted by the person.
Acute, binge-like alcohol exposure during the third-trimester-equivalent period (TTAE) produces apoptotic neurodegeneration in brain regions critical for spatial learning and memory, including the anterior thalamic nuclei (ATN), which are necessary for contextual learning and memory. To investigate the neural mechanisms underlying spatial cognition deficits following developmental alcohol exposure, we performed high-density electrophysiological recordings in and around the ATN of behaving mice, sampling 7,490 neurons across multiple, predominantly thalamic depths. To model acute binge-like TTAE, C57BL/6J mice received two injections of 2.5 g/kg ethanol (or saline) on postnatal day (PND) 7. In young adulthood (>PND 60), mice were implanted with silicon or multi-wire electrode arrays and allowed to explore a circular arena (40 cm diameter) under dim red light with two wall-mounted light-emitting diode (LED) cues that rotated pseudo-randomly. Spike timing and waveform features were extracted from each putative single unit. Across the recorded population, firing rates were generally reduced following TTAE, although responses were heterogeneous. To characterize this variability, neuronal features were embedded using uniform manifold approximation and projection (UMAP). Logistic regression classified saline- and TTAE-exposed neurons based on electrophysiological properties and UMAP coordinates, achieving 80% accuracy. Cluster-based comparisons showed weak correspondence between physiological similarity and treatment response, suggesting TTAE effects are driven primarily by anatomical location. This study presents the first large-scale in vivo electrophysiological recordings in a freely behaving mouse model of fetal alcohol spectrum disorders, revealing divergent circuit adaptations marked by hippocampal hyperexcitability and thalamic dysfunction.NEW & NOTEWORTHY The present study is one of the first to look at large-scale in vivo electrophysiological features following third-trimester equivalent alcohol exposure. By functionally grouping our neurons, we report a variety of alcohol-related deficits. One particularly striking feature is a bidirectional impact on excitability, with hippocampal neurons generally increasing their excitability and thalamic neurons generally decreasing.
Exposure to millimeter waves potentially causes pain and tissue damage at the exposed body sites. However, the threshold temperature, especially the pain threshold, remains unclear. In this study, we investigated the perception thresholds of four different types of sensations-warmth, heat, tingling, and pain-and individual physical characteristics associated with the pain perception induced by millimeter-wave exposure. Thirty-five healthy adults were exposed to a 28-GHz millimeter wave on their left middle fingertip at an input power of 8.5 W (incident power density averaged over a 1 cm2 area: 1.00 W/cm2) for up to 10 min. The temperature at which the initial subjective perception of each of the four sensation types occurred was determined as the perception threshold for that sensation. When the skin surface temperature exceeded 44°C or when the participant felt pain, the exposure was terminated. The association between participants' physical characteristics and the presence of pain was investigated using logistic regression analysis. Consequently, the perception thresholds increased in the following order: warmth < heat < tingling < pain. A total of 18 (51%) participants perceived pain, and the average pain threshold was 41.9°C. Females were more likely than males to perceive pain (odds ratio, 4.80 [1.15-20.09]), which may be partially explained by sex-related differences in hydration levels and finger circumference. Our results demonstrated that exposure to millimeter waves can induce pain at approximately 42°C and revealed clear sex differences in sensitivity to pain perception under millimeter-wave exposure.NEW & NOTEWORTHY This study investigated the perception thresholds of four types of sensations-warmth, heat, tingling, and pain-when the fingertip was exposed to 28 GHz millimeter waves. The results showed that the perception thresholds followed the order of warmth, heat, tingling, and pain, with the threshold skin temperature for pain at 41.9°C. Notably, females exhibited significantly higher sensitivity to pain than males. These findings provide further evidence supporting the need for protection from millimeter-wave exposure.
Practice enhances motor acuity, enabling movement execution with greater speed and accuracy. However, the learning principles underlying improvements in speed, accuracy, and efficiency remain relatively understudied compared with those supporting motor skill acquisition and adaptation. Here, we examined motor execution in a skill-based practice task to characterize learning, retention, and generalization of motor acuity. Using a gamified two-dimensional racing task, right-handed participants controlled a stylus-driven car along a curved track as quickly and accurately as possible. Across two studies (n = 83 total, 54 females), participants completed 300 training laps on session 1 and returned for session 2 to assess retention and generalization to novel track configurations: one with altered spatial configuration (rotated track) and one requiring movement in the opposite direction of training (reverse track). Movement speed improved rapidly, showing robust though incomplete retention across sessions. Speed improvements generalized substantially to both novel tracks. Accuracy was high at training onset and showed strong retention. However, we observed no evidence of offline gains between sessions. Notably, both speed and accuracy declined transiently for the novel track configurations compared with prior training. Movement efficiency, indexed by path length, was retained and generalized to the rotated track. However, reversing movement direction impaired efficiency, revealing a movement direction effect. This effect persisted when training direction was reversed in a second study, with counterclockwise movements remaining slower and less efficient than clockwise movements. Thus, practice produces durable and broadly transferable motor execution improvements, whereas inherent movement direction biases constrain how improvements generalize across contexts.NEW & NOTEWORTHY The learning principles underlying motor acuity improvements are relatively understudied compared with those in motor skill acquisition and adaptation. Prior work suggests that motor execution improvements show limited generalization. In contrast, we demonstrate that execution-based practice can produce robust, transferable gains, while also revealing a key constraint: inherent movement direction biases that limit generalization. By characterizing learning, retention, and generalization, this work provides insight into how motor acuity improvements compare with skill acquisition and adaptation.
Low intensity electrical stimulation of the distal tibial nerve innvervating the plantar foot with pulse trains promotes extensor activity in reduced animal preparations when delivered during the extensor phase. Since enhancing extensor activity could potentially improve weight support after spinal cord injury (SCI), we evaluated if electrical stimulation of the distal tibial nerve or its medial plantar branch enhances/prolongs extensor activity in a locomotor-trained feline model of SCI. With stimulation trains at levels activating large diameter afferents (low-threshold cutaneous/muscle group I afferents) we found no effects on the activity of the extensors and flexors during walking, whereas stimulation levels activating smaller fibers (higher-threshold cutaneous/ muscle group II) were found to increase swing height for stimuli delivered in late stance/early swing. A further increase in stimulus intensity to levels recruiting noxious afferents terminated ongoing stance and produced a flexor withdrawal response of the paw. Muscle reflex responses to low intensity single-pulse stimuli during walking showed a short-latency inhibition in extensor muscles followed by a longer latency excitatory response when stimulation was delivered during stance, and limited responses when delivered during swing. Flexors showed an early-latency excitatory response followed by a weak inhibitory response for stimulation delivered throughout most of the walking cycle. These reflex responses to single pulse stimulation agreed with prior studies. The absence of extensor activity enhancement with low-intensity train stimulation of the distal tibial nerve during stance observed in other preparations may be partially explained by changes in spinal neuronal properties and locomotor networks in chronic spinal cats.
Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels are expressed widely in various brain regions and cardiac tissue. The HCN channel conductance, named as Ih (in neurons), plays a controlling role in neuronal excitability and rhythmic oscillatory activity in individual neurons and neuronal networks. Immunohistochemical studies in the literature show HCN channel isoforms are expressed in the olfactory bulb, but relative isoform expression levels are unknown. HCN channels are encoded by four genes (HCN1-4). The expression and function of those isoforms in the five types of mitral/tufted cells are not well known. Here, we examined HCN1-4 protein and channel conductance in olfactory bulb output neurons. HCN1, 2, 3, and 4 isoforms were expressed in the olfactory bulb, with HCN4 the most abundant. HCN channel-mediated Ih conductance was present in the different classes of output neurons with the highest level in external tufted cells and low to none in mitral cells. To isolate specific contributions of the isoforms to the rhythmic firing of external tufted cells, we used cell-specific pharmacology infusing antagonists or isoform-specific blocking antisera into single neurons. Only the HCN4-blocking antisera terminated external tufted cell burst firing, whereas other antisera had no significant effect on spiking. Those results indicate that HCN4 in external tufted cells controls burst firing in these cells. Since burst firing of external tufted cells is a key regulator of activity in the olfactory bulb, this suggests HCN4 and the resulting Ih conductance are key circuit regulators.NEW & NOTEWORTHY External tufted cells in olfactory bulb are pacemaker neurons that fire rhythmic bursts. This study demonstrates that the pacemaker action of external tufted cells is critically dependent on Ih from HCN4 channel providing feedforward excitation to generate long-lasting depolarizations in the mitral cells. Since mitral/tufted cells play important roles in odor discrimination and olfactory learning, we speculate that HCN4 is a key regulatory channel in driving overall network activity and function of the olfactory bulb.
To evaluate locomotion, motorized treadmills have been widely used in research due to several advantages over conventional overground locomotion. Although comparisons have been made, whether locomotion is equivalent on the treadmill and overground at different speeds remains poorly understood. In the present study, we collected kinematic and electromyography (EMG) data in 10 intact adult cats at four matched speeds ranging from 0.5 m/s to 0.8 m/s during motorized treadmill and overground locomotion. During treadmill locomotion, fore- and hindlimb cycle and stance durations were longer, whereas swing duration was reduced at matched speeds. Cats preferred more stable support periods (i.e., with more limbs on the ground), such as triple and quadrupedal support during treadmill locomotion, whereas they favored diagonal support during overground locomotion, which is known to contribute to forward propulsion and locomotor efficiency. The type of gait and footfall pattern was conserved between locomotor tasks. The fore- and hindlimbs took longer steps and strides during overground locomotion, but paw placement at contact was more rostral during treadmill locomotion. Forelimb and hindlimb extensor muscle burst durations likely reflect the proportionally longer stance phase observed during treadmill locomotion. EMG burst amplitude was greater in fore- and hindlimb extensor muscles during overground locomotion, whereas EMG burst amplitude of flexor muscles was greater during treadmill locomotion. Overall, our findings demonstrate distinct neuromechanical strategies between treadmill and overground locomotion, reflecting differences in stability requirements, propulsion, braking, and fore- and hindlimb positioning in quadrupedal mammals.NEW & NOTEWORTHY This study provides a comprehensive comparison of treadmill and overground locomotion at different matched speeds in intact cats using kinematic and electromyographic analyses of both the forelimbs and hindlimbs. We highlight differences in locomotor strategies during treadmill and overground locomotion in both the fore- and hindlimbs. These findings demonstrate that locomotor task influences control strategies and should be carefully considered when interpreting experiments, particularly in preclinical models of spinal cord injury.
Exercise is a positive health behaviour associated with improved mood. However, the mechanisms underlying the benefits of exercise on affective health are unclear, particularly with respect to type of exercise and sex. Chronic exercise decreases neuroinflammation, which is linked to improvements in mood and anxiety. However, exercise is also a physiological stressor that can transiently upregulate systemic inflammation, and its effects on neuroinflammation are not well understood. This study examined how acute and chronic exercise affect circulating and brain cytokine levels and anxiety-related behaviour in young healthy male and female mice. In Experiment 1, mice were placed on a treadmill for a two-hour bout of moderate exercise. Two hours after exercise, animals were either tested in the open field or euthanized for measurement of cytokines (IL-1β, TNF, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IFN-γ, KC/GRO). In Experiment 2, mice underwent an 8-week moderate treadmill exercise paradigm followed by open field testing and tissue collection. Acute exercise decreased time spent in the centre of the open field in males only, suggesting increased anxiety-like behaviour in males. Acute exercise increased IL-6 and decreased TNF in serum, and increased amygdala principal component 1 (loading IL-12p70, IL-10, IFN-γ, and TNF) in both sexes. Chronic exercise increased open field centre entries, increased IL-6 in the prefrontal cortex, decreased TNF in the dorsal hippocampus, and had minimal effects on circulating cytokines in both sexes. These results demonstrate that the effects of exercise on anxiety-related behaviour and cytokine levels depend on recurrence, tissue, and brain region.
Signaling via tropomyosin-related kinase receptor B (TrkB) plays an important role in synaptic function and plasticity at the neuromuscular junction. Multiple conditions show selective effects on the most forceful and fatigable motor units that require high-frequency activation and are necessary for maximal force generation. The goal of the present study is to investigate the effects of inhibiting TrkB kinase activity on neuromuscular transmission in mouse diaphragm muscle during repeated stimulation at frequencies that reflect the recruitment of different motor units (10 vs. 75 Hz). TrkBF616A mice, which possess a mutation that renders TrkB kinase activity susceptible to rapid inhibition by 1NMPP1, were used at 6-8 mo old (n = 12; 6 females). Neuromuscular transmission failure (NMTF) was estimated in diaphragm-phrenic nerve preparations following 1 h treatment with 1NMPP1 or vehicle by assessing the difference in forces evoked by 2 min of repetitive nerve and muscle stimulation at either 10 or 75 Hz. There was no effect of 1NMPP1 on muscle contractile properties, but there was a frequency-dependent effect of 1NMPP1 treatment on the extent of NMTF. At 10-Hz stimulation, 1NMPP1 decreased the extent of NMTF compared with vehicle by 35%. At 75 Hz, 1NMPP1 increased the extent of NMTF compared with vehicle by 28%. The greater negative effect of TrkB kinase inhibition during higher-frequency stimulation suggests reliance on TrkB signaling for sustained activation predominantly at higher force, more fatigable motor units, which are responsible for the high forces necessary for airway clearance (i.e., coughing and sneezing).NEW & NOTEWORTHY This study found that inhibiting TrkB kinase activity decreases the extent of neuromuscular transmission failure during repetitive stimulation at low frequency while increasing failure with high-frequency stimulation. The frequency-dependent effect of 1NMPP1 treatment suggests that the role of TrkB signaling in maintaining neuromuscular transmission during repetitive stimulation may differ between motor unit types (slow-twitch, fatigue-resistant vs. fast-twitch, fatigable) and likely reflect effects at the presynaptic terminal without major effects on the muscle itself.
Here, we used magnetoencephalography (MEG) to investigate changes in brain functional organization and their time course following alcohol abstinence in chronic alcoholic patients. Eighteen male veterans (10 control and 8 currently alcohol-dependent) participated in this study. MEG in alcoholic participants was obtained on various days, starting at day 3 of alcohol abstinence. A MEG scan consisted of a 45-s data acquisition period from 248 whole head axial gradiometers at a frequency of 1.017 kHz. All 30,628 pairwise zero-lag cross-correlations (CC0) between prewhitened sensor time courses per scan were computed and analyzed. We found the following. At day 3 post abstinence, the mean |CC0| was 2.1× higher than that of controls, indicating a strongly hypercorrelated state. This hypercorrelation decreased gradually in a logarithmic fit, both for negative and positive CC0, which became less negative and less positive with time, respectively. These results demonstrate the power of MEG as a sensitive tool to detect, quantify, and track functional brain status during alcohol detoxification.NEW & NOTEWORTHY Here, we report on the hypercorrelation status of the chronic alcoholic brain assessed using magnetoencephalography (MEG) comprising strong negative and positive cross-correlations between 248 MEG sensors in a 45-s duration of data acquisition in the resting state. The strong correlations were reduced over time with the logarithm of the day in abstinence and were estimated to return to the levels of controls in 564-577 days, attesting to the potential for functional brain network recovery during abstinence.
Within the central auditory pathway, the inferior colliculus (IC) is a critical integration center for ascending sound information. Although IC neurons have well-characterized receptive fields for individual sound features such as sound frequency, intensity, and location, growing evidence suggests that some neurons also use multiplexing to encode sound feature combinations. Here, we performed in vivo juxtacellular recordings in awake, head-fixed mice to examine how individual IC neurons and neuronal populations encode the speed, direction, and frequency range of frequency-modulated (FM) sweeps. To understand the strategies used by neurons to represent different sound features, we trained a support vector machine to decode sound features from different parameters of the spike train, including the firing rate, spike times relative to stimulus onset, distribution of inter-spike intervals, and first spike latency. We found that many IC neurons multiplex features of FM sweeps using distinct temporal coding strategies rather than simple changes in mean firing rate, and that these feature representations are interdependent, yielding a combinatorial encoding of sound features within individual neurons. Accordingly, using static receptive fields for sweep frequency or direction alone yielded poor predictions of neuron responses to vocalizations that contain simple frequency changes. Finally, we showed that encoding strategies varied across individual neurons, resulting in a highly informative population code for FM sweep parameters. Together, our results suggest that multiplexing is a common mechanism used by IC neurons to represent complex sound features.NEW & NOTEWORTHY The inferior colliculus (IC) is a critical auditory processing center. IC neurons exhibit diverse responses to different sound features, but how IC neurons encode co-varying sound features-such as both the direction and intensity of a frequency-modulated (FM) sweep-is poorly understood. Here, we show that individual IC neurons and neuronal populations multiplex information about FM sweep direction, frequency range, and speed through distinct coding strategies, including both spike timing patterns and overall firing rate.
As a noninvasive neuromodulation technique, transcranial magnetic stimulation (TMS) offers insights into motor system physiology through motor-evoked potentials (MEPs). In the present study, we applied a factorization approach to multimuscle MEPs to characterize the pattern-level structure of corticospinal outputs beyond conventional per-muscle amplitude measures. To evaluate this approach, we analyzed multimuscle MEP datasets from three experiments in healthy young adults focusing on different stimulus parameters: stimulus intensity (experiment 1: n = 40), motor mapping size (experiment 2: n = 35), and activation of intracortical circuits by a paired-pulse TMS paradigm (experiment 3: n = 20). We extracted motor-evoked modules (MEMs) using non-negative matrix factorization (NMF) and compared their structure across different stimulus conditions. MEM structure was impacted by stimulus intensity, and these findings indicate that stimulus intensity shapes the pattern-level structure of corticospinal outputs. Varying motor mapping size had only a minor impact on MEM structure, suggesting that the pattern-level structure of corticospinal outputs elicited by TMS was stable across mapping extents. Activation of intracortical inhibition appeared to alter MEM structure compared with single-pulse TMS. These findings suggest that paired-pulse activation of intracortical inhibition may alter the pattern-level structure of corticospinal outputs. The MEM framework allows us to characterize the pattern-level structure of corticospinal outputs beyond single-muscle MEPs; thus, MEMs obtained from TMS complement well-established single-muscle MEP analyses and offer a novel perspective for investigating the motor system.NEW & NOTEWORTHY The study introduces a framework to assess the pattern-level structure of corticospinal outputs using motor-evoked modules (MEMs) obtained from transcranial magnetic stimulation (TMS). MEMs were extracted from multimuscle motor-evoked potentials (MEPs) through non-negative matrix factorization (NMF). MEM structure was impacted by stimulus intensity, and intracortical inhibition appeared to alter MEM structure compared with single-pulse TMS. The framework complements well-established single-muscle MEP analyses and offers a novel perspective for investigating the motor system.
Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea, produces a sustained sympathetically mediated increase in blood pressure. The median preoptic nucleus (MnPO) contributes to CIH-induced sympathoexcitation via projections to the paraventricular nucleus of the hypothalamus (PVN). However, the synaptic mechanisms underlying CIH-induced increased activity in this pathway remain to be determined. In addition, the impact of sex on MnPO synaptic changes in CIH exposure is unknown. We hypothesized that CIH affects MnPO synaptic activity differently between sexes and that brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) signaling plays a role in CIH-mediated changes in the MnPO-PVN pathway. We performed whole cell voltage-clamp recordings from MnPO neurons in brain slices from male and female rats exposed to either normoxia or 7 days of CIH. In PVN-projecting MnPO neurons, CIH increased mEPSC frequency only in males, while females showed a reduction in mEPSC amplitude to CIH. CIH also increased BDNF expression in the MnPO of males exposed to CIH but not in females. Pharmacological studies in male rats using K252a, K252b, and ANA-12 attenuated the CIH-induced increase in mEPSC frequency, indicating that BDNF-TrkB signaling is essential for CIH. These findings highlight a sex-specific, TrkB-dependent mechanism that enhances excitatory signaling between the MnPO and PVN. In conclusion, our study shows that PVN-projecting MnPO neurons demonstrate sex-based changes in mEPSCs and that BDNF-TrkB signaling contributes to the CIH-induced increase in mEPSC frequency in neurons from males.NEW & NOTEWORTHY Chronic intermittent hypoxia (CIH) mimics arterial hypoxemia associated with sleep apnea. These studies demonstrate that CIH produces sex-dependent changes in mEPSC properties in paraventricular nucleus (PVN) projecting median preoptic nucleus (MnPO) neurons. In neurons from male rats, BDNF contributes to CIH-induced changes in mEPSC frequency. As the PVN directly innervates the sympathetic system, this could be a possible mechanism contributing to sustained sympathoexcitation in CIH.
In rapid sequences, a fixed counting window can include spikes occurring after a neighboring contact. I reanalyzed 19,675 touches from 41 loose-seal recordings of excitatory layer 4 neurons in the public Hires et al. dataset. Spikes were recounted in windows of 10 to 50 ms around each touch. Counts after touch changed little with the preceding interval. Subtracting the rate before touch produced positive interval coefficients when close touches were retained; the coefficient approached zero when touches with preceding intervals shorter than 100 ms were excluded. Excluding each touch that had another recorded onset within 50 ms before or after it left 12,773 touches, and 12,296 entered prediction models. In trials omitted from model fitting, adding phase to timing and task variables improved prediction of spike counts by 1.5 percentage points; the improvement was 0.8 points after movement variables were included. The gain varied across analysis settings and archive subject labels, the metadata labels used to group files. The interaction between amplitude and phase added a median 0.25 points (95% confidence interval, -0.02 to 1.50). Choices of counting window altered estimates of touch history, and phase added modest predictive information after movement adjustment. Touch-spacing and counting-window checks can improve attribution in studies using rapid sensory or neuroprosthetic stimulation.NEW & NOTEWORTHY Reanalysis of active touch recordings from excitatory layer 4 neurons shows that fixed windows indexed to a target touch can include spikes occurring after neighboring contacts and alter estimates of touch history. After touches with nearby onsets were excluded, whisking phase slightly improved prediction in trials omitted from model fitting. The improvement decreased after movement variables were added. Touch-spacing and window checks reveal whether rapid sequences affect history estimates.
Acute intermittent hypoxia (AIH) elicits long-lasting increases in phrenic and sympathetic nerve activity, effects known as phrenic (pLTF) and sympathetic long-term facilitation (sympLTF), respectively. In anesthetized, paralyzed, vagotomized, and ventilated rats, pLTF magnitude following AIH consisting of 15, 1-min isocapnic hypoxic episodes (i.e., 15x1) is greater during the mid-rest versus mid-active phase of the diurnal cycle. However, it is unknown if sympLTF exhibits similar diurnal regulation. In urethane-anesthetized, mechanically ventilated, male Sprague-Dawley rats, we hypothesized that sympLTF elicited by 15x1 AIH ([Formula: see text] 40-55 mmHg) is greater in the mid-rest than in mid-active diurnal phase. We report renal sympathetic nerve activity (RSNA) remained elevated 90 min post-AIH, with similar responses in mid-rest (n = 20) versus mid-active phase rats (n = 17). No significant increase was observed in time control rats in either mid-rest (n = 10) or mid-active phase (n = 9). Mean ΔRSNA (%) was 142 ± 184 during mid-rest AIH and 101 ± 124 during mid-active AIH, versus 34 ± 28 and 28 ± 52 in corresponding mid-rest and mid-active time controls. There was a significant main effect of AIH on ΔRSNA (%) (P = 0.020), with no effect of time of day (P = 0.544) and no interaction (P = 0.644). Increases in RSNA following AIH were driven primarily by increases in burst amplitude and duration, with minimal changes in burst frequency. Furthermore, mean arterial pressure did not change from baseline in any group (all P > 0.05). These findings demonstrate that AIH elicits modest increases in RSNA that are not accompanied by increases in arterial pressure and are not modulated by time of day, contrasting with the diurnal regulation of pLTF.NEW & NOTEWORTHY Acute intermittent hypoxia (AIH) is widely reported to elicit plasticity in sympathetic nerve activity in anesthetized, vagotomized rats. Here, we demonstrate that, in vagal-intact rats, only modest renal sympathetic nerve plasticity occurs (without change in mean arterial pressure) in response to AIH delivery in the diurnal rest or active phase. Similarity in AIH-induced renal sympathetic nerve plasticity versus time-dependent drift in sham rats highlights the need for careful experimental controls in studies of sympathetic plasticity.
Bilateral deficit, reduced performance during bimanual movements relative to unimanual execution, has been consistently reported in healthy individuals, yet whether this effect is uniform across hands remains unclear. We examined hand-specific bilateral effects during maximal-speed cyclic finger movements in 73 right-handed participants across unimanual, bimanual in-phase, and bimanual anti-phase coordination conditions. The dominant hand exhibited bilateral deficit, whereas the nondominant hand demonstrated facilitation during in-phase coordination. Anti-phase coordination significantly reduced frequency in both hands, accompanied by increased movement amplitude. Multivariate regression analysis revealed a hand-specific dissociation; unimanual frequency asymmetry predicted dominant hand deficit, whereas amplitude modulation predicted nondominant hand facilitation. These opposing effects align with complementary hemispheric specialization and asymmetric interhemispheric interactions during synchronization. An extended coupled oscillator model incorporating hand-specific natural frequencies predicted these asymmetric effects through weighted frequency convergence during in-phase coordination and amplitude-dependent stability constraints during anti-phase coordination, with predictions consistent with the experimental observations. These findings demonstrate that bilateral deficit and facilitation can coexist within the same individual, with implications for understanding asymmetric limb function and for theoretical models of bimanual coordination.NEW & NOTEWORTHY Bilateral coordination produces asymmetric, hand-specific effects rather than a uniform bilateral deficit. The dominant hand exhibited bilateral deficit, while the nondominant hand demonstrated facilitation during in-phase coordination. Unimanual frequency asymmetry and amplitude modulation differentially predicted these opposing effects, suggesting distinct hemispheric contributions to bimanual performance. An extended coupled oscillator model incorporating hand-specific natural frequencies successfully captured these asymmetric patterns through weighted frequency convergence and amplitude-dependent stability.
