High Levels Of Spontaneous Activity Research Articles

Self-esteem mediates the relationship between the parahippocampal gyrus and decisional procrastination at resting state.

When faced with a conflict or dilemma, we tend to postpone or even avoid making a decision. This phenomenon is known as decisional procrastination. Here, we investigated the neural correlates of this phenomenon, in particular the parahippocampal gyrus (PHG) that has previously been identified in procrastination studies. In this study, we applied an individual difference approach to evaluate participants' spontaneous neural activity in the PHG and their decisional procrastination levels, assessed outside the fMRI scanner. We discovered that the fractional amplitude of low-frequency fluctuations (fALFF) in the caudal PHG (cPHG) could predict participants' level of decisional procrastination, as measured by the avoidant decision-making style. Importantly, participants' self-esteem mediated the relationship between the cPHG and decisional procrastination, suggesting that individuals with higher levels of spontaneous activity in the cPHG are likely to have higher levels of self-esteem and thus be more likely to make decisions on time. In short, our study broadens the PHG's known role in procrastination by demonstrating its link with decisional procrastination and the mediating influence of self-esteem, underscoring the need for further exploration of this mediation mechanism.

Creatine Supplementation Alleviates Fatigue after Exercise through Anti-Inflammatory Action in Skeletal Muscle and Brain

Eccentric exercise induces muscle damage and inflammation, resulting in a state of reduced physical activity with muscle dysfunction and a feeling of tiredness after exercise. Creatine is known to act as an energy buffer, but it has also been suggested to exert inhibitory effects on muscle damage and peripheral inflammation. The purpose of this study was to test the hypothesis that creatine supplementation alleviates fatigue after eccentric exercise and to explore the mechanism of this effect. C57BL/6J mice were fed an AIN-93G-formulated control diet or a creatine-containing diet for 6 days and were then subjected to downhill running, a model of eccentric exercise, to assess the effects on the total creatine concentrations in skeletal muscle and brain tissue, spontaneous activity, the urine concentration of titin N-fragment, and inflammatory gene expression. The results showed that creatine supplementation significantly increased the total creatine concentrations in skeletal muscle and brain tissue. Furthermore, spontaneous activity significantly decreased after downhill running and creatine supplementation maintained a significantly higher level of spontaneous activity. In addition, creatine supplementation significantly suppressed the downhill-running-induced increase in the mRNA expression of genes encoding ICAM-1, E-selectin, CD18, and BKB1R in the soleus muscle and IL-1β in the hypothalamus. On the other hand, creatine supplementation did not clearly influence the urine concentration of titin N-fragment. These results indicate that creatine supplementation may alleviate fatigue after eccentric exercise by partially suppressing inflammation in slow-twitch skeletal muscle and brain tissue.

HSPGs glypican-1 and glypican-4 are human neuronal proteins characteristic of different neural phenotypes.

Generating neurons from human stem cells has potential for brain damage therapy and neurogenesis modeling, but current efficacy is limited by culture heterogeneity and the lack of markers. We have previously reported the heparan sulfate proteoglycans (HSPGs) glypican-1 (GPC1) and -4 (GPC4) as the markers of lineage-specific human neural stem cells (hNSCs) and mediators of hNSC lineage potential. Here, we further examined phenotypical characteristics and GPC1 and GPC4 during neural differentiation of hNSCs in the presence of two neurogenic growth factors reported to bind to heparan sulfate: brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor-B (PDGF-B). In hNSC neural cultures, GPC1 and GPC4 were expressed along neurites and cell bodies in long-term (40-60days) neural differentiation cultures demonstrating the areas of differential localization-suggesting potentially different functions. Neural differentiation cultures in the presence of BDNF or PDGF-B generated phenotypically different neural cells with BDNF treatment associated with higher GPC4 versus GPC1 expression, increased heterogeneity, and differential neuron subtype marker expression to PDGF-B cultures. PDGF-B cultures exhibited higher levels of spontaneous activity and reduced heterogeneity over long-term culture associated with decreased GPC4. Untreated neural cultures were highly variable, supporting the use of neuroregulatory growth factors for guided differentiation. Targeted siRNA downregulation of GPC1/4 reduced neural differentiation markers and altered response to exogenous BDNF and PDGF-B. This work confirms GPC1 and GPC4 as regulators of human neural differentiation and supports their use as novel markers of neural cell characterization.

Low-Intensity Running and High-Intensity Swimming Exercises Differentially Improve Energy Metabolism in Mice With Mild Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA), an autosomal recessive neurodegenerative disease characterized by the loss of spinal-cord motor-neurons, is caused by mutations on Survival-of-Motor Neuron (SMN)-1 gene. The expression of SMN2, a SMN1 gene copy, partially compensates for SMN1 disruption due to exon-7 excision in 90% of transcripts subsequently explaining the strong clinical heterogeneity. Several alterations in energy metabolism, like glucose intolerance and hyperlipidemia, have been reported in SMA at both systemic and cellular level, prompting questions about the potential role of energy homeostasis and/or production involvement in disease progression. In this context, we have recently reported the tolerance of mild SMA-like mice (SmnΔ7/Δ7; huSMN2+/+) to 10 months of low-intensity running or high-intensity swimming exercise programs, respectively involving aerobic and a mix aerobic/anaerobic muscular metabolic pathways. Here, we investigated whether those exercise-induced benefits were associated with an improvement in metabolic status in mild SMA-like mice. We showed that untrained SMA-like mice exhibited a dysregulation of lipid metabolism with an enhancement of lipogenesis and adipocyte deposits when compared to control mice. Moreover, they displayed a high oxygen consumption and energy expenditure through β-oxidation increase yet for the same levels of spontaneous activity. Interestingly, both exercises significantly improved lipid metabolism and glucose homeostasis in SMA-like mice, and enhanced oxygen consumption efficiency with the maintenance of a high oxygen consumption for higher levels of spontaneous activity. Surprisingly, more significant effects were obtained with the high-intensity swimming protocol with the maintenance of high lipid oxidation. Finally, when combining electron microscopy, respiratory chain complexes expression and enzymatic activity measurements in muscle mitochondria, we found that (1) a muscle-specific decreased in enzymatic activity of respiratory chain I, II, and IV complexes for equal amount of mitochondria and complexes expression and (2) a significant decline in mitochondrial maximal oxygen consumption, were reduced by both exercise programs. Most of the beneficial effects were obtained with the high-intensity swimming protocol. Taking together, our data support the hypothesis that active physical exercise, including high-intensity protocols, induces metabolic adaptations at both systemic and cellular levels, providing further evidence for its use in association with SMN-overexpressing therapies, in the long-term care of SMA patients.

Neurons derived from induced pluripotent stem cells on microelectrode arrays: a human model for neurodevelopmental disorders

Neurons derived from induced pluripotent stem cells on microelectrode arrays: a human model for neurodevelopmental disorders

Behavioural modification of personality traits: testing the effect of a trematode on nymphs of the red damselfly Xanthocnemis zealandica.

Research on animal personality is increasingly demonstrating that individuals in a population are characterised by distinct sets of behavioural traits that show consistency over time and across different situations. Parasites are known to alter the behaviour of their hosts, although their role in shaping host personality remains little studied. Here, we test the effect of trematode infection on two traits of their host's personality, activity and boldness, in nymphs of the red damselfly Xanthocnemis zealandica. Genetic analyses indicate that the undescribed trematode species falls within the superfamily Microphalloidea. Results of laboratory behavioural tests indicate that the two behavioural traits are related to each other: bolder individuals also show higher levels of spontaneous activity than shy ones. However, parasite infection had no effect on either of these behaviours or on their repeatability over three separate testing sessions. Although our findings suggest that this trematode does not influence personality traits of the damselfly host, it remains possible that other standard personality traits not tested here (exploratory tendency, aggressiveness) are affected by infection.

Spontaneous activity is correlated with coding density in primary auditory cortex.

Sensory neurons across sensory modalities and specific processing areas have diverse levels of spontaneous firing rates (SFRs) in the absence of sensory stimuli. However, the functional significance of this spontaneous activity is not well-understood. Previous studies in the auditory system have demonstrated that different levels of spontaneous activity are correlated with a variety of physiological and anatomic properties, suggesting that neurons with differing SFRs make unique contributions to the encoding of auditory stimuli. Additionally, altered SFRs are a correlate of tinnitus, arising in several auditory areas after exposure to ototoxic substances and noise trauma. In this study, we recorded single-unit activity from primary auditory cortex of awake marmoset monkeys while delivering wide-band random-spectrum stimuli and white Gaussian noise (WGN) to examine any divergences in stimulus encoding properties across SFR classes. We found that higher levels of spontaneous activity were associated with both higher levels of activation relative to suppression across a variety of wide-band stimuli and higher driven rates in response to WGN. Moreover, response latencies to WGN were negatively correlated with the level of activation in response to both stimulus types. These findings are consistent with a novel view of the role spontaneous spiking may play during normal stimulus processing in primary auditory cortex and how it may malfunction in cases of tinnitus.

Expression of c‐fos in hilar mossy cells of the dentate gyrus in vivo

Granule cells (GCs) of the dentate gyrus (DG) are considered to be quiescent--they rarely fire action potentials. In contrast, the other glutamatergic cell type in the DG, hilar mossy cells (MCs) often have a high level of spontaneous activity based on recordings in hippocampal slices. MCs project to GCs, so activity in MCs could play an important role in activating GCs. Therefore, we investigated whether MCs were active under basal conditions in vivo, using the immediate early gene c-fos as a tool. We hypothesized that MCs would exhibit c-fos expression even if rats were examined randomly, under normal housing conditions. Therefore, adult male rats were perfused shortly after removal from their home cage and transfer to the laboratory. Remarkably, most c-fos immunoreactivity (ir) was in the hilus, especially temporal hippocampus. C-fos-ir hilar cells co-expressed GluR2/3, suggesting that they were MCs. C-fos-ir MCs were robust even when the animal was habituated to the investigator and laboratory where they were euthanized. However, c-fos-ir in dorsal MCs was reduced under these circumstances, suggesting that ventral and dorsal MCs are functionally distinct. Interestingly, there was an inverse relationship between MC and GC layer c-fos expression, with little c-fos expression in the GC layer in ventral sections where MC expression was strong, and the opposite in dorsal hippocampus. The results support the hypothesis that a subset of hilar MCs are spontaneously active in vivo and provide other DG neurons with tonic depolarizing input.

Physical Activity and Physical Function in Older Adults With Knee Osteoarthritis

To assess correlates of physical activity, and to examine the relationship between physical activity and physical functioning, in 160 older (66 ± 6 years old), overweight/obese (mean body mass index = 33.5 ± 3.8 kg/m2), sedentary (less than 30 mins of activity, 3 days a week) individuals with knee osteoarthritis. Physical activity was measured with accelerometers and by self-report. Physical function was assessed by 6-min walk distance, knee strength, and the Short Physical Performance Battery. Pain and perceived function were measured by questionnaires. Pearson correlations and general linear models were used to analyze the relationships. The mean number of steps taken per day was 6209 and the average PAEE was 237 ± 124 kcal/day. Participants engaged in 131 ± 39 minutes of light physical activity (LPA) and 10.6 ± 8.9 minutes of moderate-vigorous physical activity (MPA/VPA). Total steps/day, PAEE, and minutes of MPA/VPA were all negatively correlated with age. The 6-min walk distance and lower extremity function were better in those who had higher total steps/day, higher PAEE, higher minutes of MPA/VPA, and a higher PASE score. This study demonstrates that a population who has higher levels of spontaneous activity have better overall physical function than those who engage in less activity.

The influence of spontaneous activity on stimulus processing in primary visual cortex

Spontaneous activity in the resting human brain has been studied extensively; however, how such activity affects the local processing of a sensory stimulus is relatively unknown. Here, we examined the impact of spontaneous activity in primary visual cortex on neuronal and behavioural responses to a simple visual stimulus, using functional MRI. Stimulus-evoked responses remained essentially unchanged by spontaneous fluctuations, combining with them in a largely linear fashion (i.e., with little evidence for an interaction). However, interactions between spontaneous fluctuations and stimulus-evoked responses were evident behaviourally; high levels of spontaneous activity tended to be associated with increased stimulus detection at perceptual threshold. Our results extend those found in studies of spontaneous fluctuations in motor cortex and higher order visual areas, and suggest a fundamental role for spontaneous activity in stimulus processing.

Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model

Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors.

Aging affects contrast response functions and adaptation of middle temporal visual area neurons in rhesus monkeys

In the present study we studied the effects of aging on the coding of contrast in area V1 (primary visual cortex) and MT (middle temporal visual area) of the macaque monkey using single-neuron in vivo electrophysiology. Our results show that both MT and V1 neurons in old monkeys are less sensitive to contrast than those in young monkeys. Generally, contrast sensitivity is affected by aging more severely in MT cells than in V1 cells. Specifically, MT cells were affected more severely than motion direction selective V1 cells. Particularly, we found that MT neurons in old monkeys exhibited enhanced maximum visual responses, higher levels of spontaneous activity and decreased signal-to-noise ratios. In addition, we also found age-related changes in neuronal adaptation to visual motion in MT. Compared with young animals, the contrast gain of MT neurons in old monkeys is less affected, but the response gain by adaptation of MT neurons is more affected. Our results suggest that there may be an anomalous visual processing in both the magnocellular and parvocellular pathways. The neural changes described here are consistent with an age-related degeneration of intracortical inhibition and could underlie some deficits in visual function during normal aging.

Differential Attention-Dependent Response Modulation across Cell Classes in Macaque Visual Area V4

The cortex contains multiple cell types, but studies of attention have not distinguished between them, limiting understanding of the local circuits that transform attentional feedback into improved visual processing. Parvalbumin-expressing inhibitory interneurons can be distinguished from pyramidal neurons based on their briefer action potential durations. We recorded neurons in area V4 as monkeys performed an attention-demanding task. We find that the distribution of action potential durations is strongly bimodal. Neurons with narrow action potentials have higher firing rates and larger attention-dependent increases in absolute firing rate than neurons with broad action potentials. The percentage increase in response is similar across the two classes. We also find evidence that attention increases the reliability of the neuronal response. This modulation is more than two-fold stronger among putative interneurons. These findings lead to the surprising conclusion that the strongest attentional modulation occurs among local interneurons that do not transmit signals between areas.

The association between t‐type Ca2+ current and outward current in isolated human detrusor cells from stable and overactive bladders

To determine if bladder overactivity in humans is associated with an altered activity of Ca(2+) channels in detrusor smooth muscle and the consequent activation of other ion channels. Samples of bladder were obtained from patients with urodynamically stable bladders, or with idiopathic detrusor overactivity. Isolated cells were patch-clamped with pipettes containing a Cs(+)-based filling solution to isolate inward currents, or a K(+)-filling solution to measure outward current. Components of inward current were separated according to their sensitivity to NiCl(2) (< or =100 microm) and nifedipine. Ni(2+)-sensitive (T-type) and nifedipine-sensitive (L-type) current was recorded in all cells. The voltage- and time-dependent properties were similar in cells from both patient groups. However, the current density of the L-type current was less, and that of the T-type current was greater, in myocytes from overactive bladders. In cells from overactive bladders, the mean K(+) current over the range - 80 to - 50 mV was also higher than in control cells. This current was sensitive to the large-conductance channel modulator iberiotoxin and to NiCl(2) (100 microm) Detrusor myocytes from overactive human bladders have a higher T-type Ca(2+) current density; we propose that this increases transient outward currents, and so might contribute to higher levels of spontaneous activity.

Dynamic Encoding of Amplitude-Modulated Sounds at the Level of Auditory Nerve Fibers

The relationship between the mean spike frequency of auditory nerve fibers and the levels of tonal stimuli with frequencies equal to the characteristic frequency can be presented as the "input-output" characteristic. In real auditory nerve fibers, the slope of this characteristic increases and its width decreases with increases in the level of spontaneous activity or the ability of fibers to generate spikes in the absence of a stimulus. However, real fibers with low spontaneous activity reproduce the amplitude modulation of sinusoidally amplitude-modulated signal significantly better than fibers with high levels of spontaneous activity. The simulation experiment reported here shows that the reason for the good reproduction of amplitude modulation in auditory nerve fibers is not the static profiles of the "input-output" characteristic but the dynamic properties of fibers which support the tuning (adaptation) of the threshold of the fiber to the level of the stimulus being applied. Because of their steep "input-output" characteristic, auditory nerve fibers with high levels of spontaneous activity can reproduce the modulation of sounds at subthreshold levels when a weak noise is added to the signal, thus demonstrating the property of stochastic resonance.

Exciting Inhibition

Some neurons exhibit high levels of spontaneous activity, allowing synaptic input to "tune" the system either up or down, that is, to increase or decrease the activity of these spontaneously firing neurons (see Häusser and Monsivais). Nelson et al. examined the plasticity of the spontaneously active neurons of the medial vestibular nucleus (MVN), which is responsible for the vestibulo-ocular reflex that stabilizes images on the retina during head movement by altering the rate of eye movements. In MVN slices, transient activation of inhibitory synaptic input leads to prolonged increase in spontaneous firing rate and in the "gain" of the firing response (slope of the relationship between the input current and the firing rate) once inhibitory input is terminated, a response termed firing rate potentiation (FRP). FRP was also produced in response to application of the inhibitory transmitters γ-aminobutyric acid and glycine, and in response to direct hyperpolarization by current injection. Synaptic inhibition produced a decrease in afterhyperpolarization (AHP), a change in membrane potential mediated by potassium currents; thus, it implicated potassium channels as participating in FRP. Stimuli that produced FRP also decreased intracellular calcium concentration, and transient depletion of calcium by application of a calcium chelator or by transient removal from the extracellular medium also triggered FRP. Inhibition of calcium-activated potassium channels could account for the change in AHP and contribute to the induction of FRP. Pharmacological inhibition of either the SK or BK channels stimulated FRP; however, only when BK channels were inhibited was hyperpolarization of the neurons unable to trigger further FRP. Thus, decreased calcium leading to inhibition of BK channels appears to be central to the inhibition-mediated stimulation of spontaneous activity. A. B. Nelson, C. M. Krispel, C. Sekirnjak, S. du Lac, Long-lasting increases in intrinsic excitability triggered by inhibition. Neuron 40 , 609-620 (2003). [Online Journal] M. Häusser, P. Monsivais, Less means more: Inhibition of spontaneous firing triggers persistent increases in excitability. Neuron 40 , 449-450 (2003). [Online Journal]

Exciting Inhibition

Some neurons exhibit high levels of spontaneous activity, allowing synaptic input to "tune" the system either up or down, that is, to increase or decrease the activity of these spontaneously firing neurons (see Häusser and Monsivais). Nelson et al. examined the plasticity of the spontaneously active neurons of the medial vestibular nucleus (MVN), which is responsible for the vestibulo-ocular reflex that stabilizes images on the retina during head movement by altering the rate of eye movements. In MVN slices, transient activation of inhibitory synaptic input leads to prolonged increase in spontaneous firing rate and in the "gain" of the firing response (slope of the relationship between the input current and the firing rate) once inhibitory input is terminated, a response termed firing rate potentiation (FRP). FRP was also produced in response to application of the inhibitory transmitters γ-aminobutyric acid and glycine, and in response to direct hyperpolarization by current injection. Synaptic inhibition produced a decrease in afterhyperpolarization (AHP), a change in membrane potential mediated by potassium currents; thus, it implicated potassium channels as participating in FRP. Stimuli that produced FRP also decreased intracellular calcium concentration, and transient depletion of calcium by application of a calcium chelator or by transient removal from the extracellular medium also triggered FRP. Inhibition of calcium-activated potassium channels could account for the change in AHP and contribute to the induction of FRP. Pharmacological inhibition of either the SK or BK channels stimulated FRP; however, only when BK channels were inhibited was hyperpolarization of the neurons unable to trigger further FRP. Thus, decreased calcium leading to inhibition of BK channels appears to be central to the inhibition-mediated stimulation of spontaneous activity.A. B. Nelson, C. M. Krispel, C. Sekirnjak, S. du Lac, Long-lasting increases in intrinsic excitability triggered by inhibition. Neuron 40, 609-620 (2003). [Online Journal]M. Häusser, P. Monsivais, Less means more: Inhibition of spontaneous firing triggers persistent increases in excitability. Neuron 40, 449-450 (2003). [Online Journal]

Neuropeptide expression following ligation of the ferret lingual nerve

Previous studies on the ferret inferior alveolar nerve found a close association between the spontaneous neural activity generated at a site of nerve injury, and the accumulation of neuropeptides in the injured axons. More recent electrophysiological studies on the lingual nerve revealed high levels of spontaneous activity 3 days after injury, a decline at 3 weeks and a late rise at 3 months. In the present study we have used immunocytochemical techniques to see whether this time course of spontaneous activity is again paralleled by an accumulation of neuropeptides. In 20 anaesthetised adult ferrets the left lingual nerve was ligated and sectioned distally, and the animals left to recover for 3 days, 3 weeks or 3 months. The tissue was processed using indirect immunofluorescence and image analysis was used to quantify levels of the neuropeptides; calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), enkephalin (ENK) and neuropeptide Y (NPY). Immunoreactivity to all of the neuropeptides was present proximal to the ligature 3 days after injury, and these high levels of expression had decreased considerably by 3 weeks. By 3 months ENK and NPY expression had almost disappeared proximal to the ligature, but levels of CGRP, SP, VIP and GAL had increased slightly. This was also accompanied by an accumulation of all of the neuropeptides, except NPY, in the portion of nerve immediately distal to the ligature. This late accumulation of certain neuropeptides coincides with the increase in spontaneous activity seen in our previous electrophysiological studies and supports the suggestion that neuropeptides may play a role in the aetiology of sensory disorders after nerve injury.

Weak electric field interactions in the central nervous system.

Exposure to extremely low frequency electric and magnetic fields will induce electric fields and currents within the body, but these are almost always much lower than those that can stimulate peripheral nerve tissue. Guidance on exposure to such fields has been published by NRPB and ICNIRP, which is based on the avoidance of acute effects in the central nervous system. Weak electric field effects, below action potential thresholds, have been demonstrated in vitro in brain slice preparations; thresholds can be estimated to be above about 1 mV mm(-1) (around 100 mA m(-2), taking a brain tissue conductivity of around 0.1 S m(-1)), depending on stimulus conditions. Some studies suggest possible effects at lower induced field strengths. The intact nervous system might be expected to be more sensitive to induced electric fields and currents than in vitro preparations, due to a higher level of spontaneous activity and a greater number of interacting neurons. There is good evidence that electrically excitable cells in the retina can be affected in vivo by induced currents as low as 10 mA m(-2). It has been suggested that induced current densities above 10 mA m(-2) may have effects on other central nervous system functions but few studies have been carried out. Further research in experimental animals using both in vitro and in vivo approaches is needed to clarify this issue.

Calcitonin gene-related peptide modifies the ectopic discharge from damaged nerve fibres in the ferret

Previous studies in our laboratory have shown that the neuropeptide, calcitonin gene-related peptide (CGRP) accumulates at a site of inferior alveolar nerve injury at the time when high levels of spontaneous activity and mechanical sensitivity are recorded electrophysiologically. The present study was undertaken to determine whether or not the CGRP could be playing a role in initiating or modulating the neuronal activity. In 18 anaesthetised adult ferrets the left inferior alveolar nerve was sectioned and ligated and recovery permitted for 3 days. Under a second anaesthetic recordings were made from a fine nerve filament, containing up to four active or silent units, dissected from the nerve proximal to the injury. After recording activity for a 30 min control period, CGRP and then the CGRP antagonist (CGRP 8–37) were applied either by close-arterial injection or topically (10 −4 M, 0.2 ml). After each application activity was recorded for a 30 min period. Recordings were made from 52 units, of which 26 (50%) were spontaneously active and 30 (58%) were mechanically sensitive. The spontaneous activity in five units was increased by the application of CGRP, and the CGRP antagonist subsequently reduced the activity in two of these units. Activity was induced by CGRP in three previously silent units. Overall, activity was affected in 19% of the units studied. We conclude that CGRP present within a neuroma may initiate or modulate the level of ectopic discharge from some damaged nerve fibres and therefore may contribute to the sensory disturbances which follow nerve injury.