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Electrophysiological properties of cortically projecting histamine neurons of the rat hypothalamus.

The tuberomammillary (TM) nuclei of the hypothalamus appear to be the sole histaminergic cell group in the brain. The extracellular electrophysiological properties of cortically projecting TM neurons were studied in the urethane-anesthetized rat. TM neurons, antidromically activated from either ipsi- or contralateral cerebral cortex, displayed relatively slow conduction velocities, consistent with reports suggesting that TM neurons possess unmyelinated axons. Spontaneous activity was slow and regular, with action potentials of long duration. There was often a noticeable delay between initial segment and somatodendritic portions of spontaneous action potentials, and complete loss of the somatodendritic portion of the second antidromic action potential was commonly seen when double pulse paradigms were employed. These data demonstrate that in addition to anatomical and biochemical similarities, TM neurons share a constellation of physiological properties with other central aminergic neurons.

Action Potentials↗

[The brain and the pain: neurotransmitters and neuronal pathways of pain perception and response].

The pain, an unpleasant feeling, induces several central nervous system mechanisms, like sensory-discriminative, motivational-affective activities, behavioral changes and it activates various responses, including antinociceptive actions. Accordingly, signals from the nociceptive neurons in the spinal cord and the sensory trigeminal nucleus ascend in various neuronal pathways and target several brain areas. Here, five ascending pain-conducting neuronal pathways and two spinal reflex routes are briefly summarized. The spinal and supraspinal antinociceptive mechanisms are described in more detail. During the past two decades, endogenous opioids, cannabinoids and their receptors have been discovered, localized and cloned. Five groups of endogenous opiates are known: beta-endorphin, enkephalins, dynorphins, endomorphins, and nociceptin. Two endogenous cannabinoids have already been described in the brain: the anandamide and the 2-arachidonyl-glycerol. The site of their antinociceptive (analgesic) actions in the brain are briefly summarized.

Afferent Pathways↗

Response characterstics of spinothalamic tract neurons that project to the posterior thalamus in rats.

A sizeable number of spinothalamic tract axons terminate in the posterior thalamus. The functional roles and precise areas of termination of these axons have been a subject of recent controversy. The goals of this study were to identify spinothalamic tract neurons (STT) within the cervical enlargement that project to this area, characterize their responses to mechanical and thermal stimulation of their receptive fields, and use microantidromic tracking methods to determine the nuclei in which their axons terminate. Forty-seven neurons were antidromically activated using low-amplitude (< or =30 microA) current pulses in the contralateral posterior thalamus. The 51 points at which antidromic activation thresholds were lowest were surrounded by ineffective tracks indicating that the surrounded axons terminated within the posterior thalamus. The areas of termination were located primarily in the posterior triangular, medial geniculate, posterior and posterior intralaminar, and suprageniculate nuclei. Recording points were located in the superficial and deep dorsal horn. The mean antidromic conduction velocity was 6.4 m/s, a conduction velocity slower than that of other projections to the thalamus or hypothalamus in rats. Cutaneous receptive fields appeared to be smaller than those of neurons projecting to other areas of the thalamus or to the hypothalamus. Each of the examined neurons responded exclusively or preferentially to noxious stimuli. These findings indicate that the STT carries nociceptive information to several target nuclei within the posterior thalamus. We discuss the evidence that this projection provides nociceptive information that plays an important role in fear conditioning.

Action Potentials↗

Unusual neurophysiological features in Cockayne's syndrome: a report of two cases as a contribution to diagnosis and classification.

To clarify the diagnostic value of neurophysiological investigations in patients with Cockayne's syndrome (CS). The study involved two patients with clinical diagnoses of classical and severe CS, who were neurophysiologically evaluated by means of: (1) multimodal visual (VEPs), brainstem auditory (BAEPs) and upper limb somatosensory (SEPs) evoked potentials; (2) electroretinography; and (3) nerve conduction and needle electromyography studies. Both patients showed multimodal evoked potential (EP) signs of central nervous system involvement that overlapped in severity and extent, and were consistent with demyelination along the central sensory pathways. Flash VEPs and SEPs were more altered than pattern VEPs and BAEPs. No signs of retinopathy or hearing loss of cochlear origin were detected. The nerve conduction and needle electromyography studies showed severe signs of sensory and motor demyelinating and axonal peripheral neuropathy. Peripheral neuropathy was clinically uncertain. There were no significant differences between the two patients. Our results show that combined multimodal EP and nerve conduction studies are diagnostically highly sensitive even in the early stage of CS, but their ability to distinguish classical and severe CS is limited. The unusual features were characterised by the absence of clinical and electrophysiological signs of otherwise common retinopathy and neurosensory hearing loss. BAEPs seem to be more useful than VEPs or SEPs in the diagnostic work-up of patients with suspected CS.

Central Nervous System↗

[Vagal thermoreceptors in the gastro-intestinal area. Their role in the regulation of the digestive motility (author's transl)].

In anaesthetized cats, sensory vagal units were recorded in the nodose ganglion by means of extracellular glass microelectrodes. In the antrum and the duodenum we have found receptors tonically activated by warm (38-51 degrees C with an optimum at 46-49 degrees C) or cold (36-10 degrees C with an optimum at 12-10 degrees C) solutions. These receptors did not respond to mechanical stimuli (compression and distension of the viscera) and to chemical ones (perfusion with glucose and acid solutions). Thus they did not belong to polymodal type, but they must be considered as true thermoreceptors, specifically sensitive to warm or cold stimulations. The gastro-duodenal thermoreceptors were connected to non-medullated vagal fibres (conduction velocity: 0.8-1.4 m/s). On the other hand, the role of the gastro-duodenal vagal thermoreceptors in the regulation of the digestive motility was studied. By using several electromyographic recordings, it was possible to show that the cold and warm stimulations of the duodenum which elicited thermoreceptor responses, induced an inhibition of the electrical activity of the antrum. The changes persisted after bisplanchnectomy, but disappeared completely after bivagotomy. From these facts it was concluded that the vagal thermoreceptors were involved in the nervous regulations of the gastro-duodenal motility.

Animals↗

Two bidirectional nerve cord systems converging with electrical and chemical synapses on the Retzius cells of the leech Hirudo Medicinalis.

Electrical stimulation of the ventral cord of H. medicinalis elicits in both Retzius' cells of each segmental ganglion an EPSP which is composed by an early and a late component. The early EPSP is electrical in nature, since it is unaffected by displacements of the membrane potential and by high Mg2+, whereas the late one is chemical, being reversed in sign by membrane depolarization and suppressed by high Mg2+. Latency measurements show that the electrical and chemical EPSP components are mediated by two different pathways characterized by conduction velocities of 0.5 and 0.3 m/sec respectively. Both pathways run in each of the lateral connectives and propagate impulses in anterior and posterior direction. Collision experiments show that ascending and descending impulses along the pathway mediating the electrical EPSP travel along the same fibres. Separate stimulation of the lateral connectives and selective inactivation of one Retzius' cell show that both pathways converge onto each Retzius' cell show that both pathways converge onto each Retzius cell. The possible functional significance of the two excitatory pathways is discussed.

Animals↗

Well-timed, brief inhibition can promote spiking: postinhibitory facilitation.

Brief synaptic inhibition can overwhelm a nearly coincident suprathreshold excitatory input to preclude spike generation. Surprisingly, a brief inhibitory event that occurs in a favorable time window preceding an otherwise subthreshold excitation can facilitate spiking. Such postinhibitory facilitation (PIF) requires that the inhibition has a short (decay) time constant tauinh. The timescale ranges of tauinh and of the window (width and timing) for PIF depend on the rates of neuronal subthreshold dynamics. The mechanism for PIF is general, involving reduction by hyperpolarization of some excitability-suppressing factor that is partially recruited at rest. Here we illustrate and analyze PIF, experimentally and theoretically, using brain stem auditory neurons and a conductance-based five-variable model. In this auditory case, PIF timescales are in the sub- to few millisecond range and the primary mechanistic factor is a low-threshold potassium conductance gKLT. Competing dynamic influences create the favorable time window: hyperpolarization that moves V away from threshold and hyperexcitability resulting from reduced gKLT. A two-variable reduced model that retains the dynamics only of V and gKLT displays a similar time window. We analyze this model in the phase plane; its geometry has generic features. Further generalizing, we show that PIF behavior may occur even in a very reduced model with linear subthreshold dynamics, by using an integrate-and-fire model with an accommodating voltage-dependent threshold. Our analyses of PIF provide insights for fast inhibition's facilitatory effects in longer trains. Periodic subthreshold excitatory inputs can lead to firing, even one for one, if brief inhibitory inputs are interleaved within a range of favorable phase lags. The temporal specificity of inhibition's facilitating effect could play a role in temporal processing, in sensitivity to inhibitory and excitatory temporal patterning, in the auditory and other neural systems.

Action Potentials↗

A new method to determine pudendal nerve motor latency and central motor conduction time to the external anal sphincter.

By placing the earth electrode between the site of the stimulus and the site of derivation, peripheral motor latency to the external anal sphincter can be determined and thus central motor conduction time (CMCT) can be calculated. In 18 volunteers we found a total motor conduction time of 19.4 msec (S.D. 1.71) after stimulation of the motor cortex and recording above the external anal sphincter. Latency was 5.6 msec (S.D. 0.66) when stimulated above L1 and pudendal latency (MEPuL) after stimulation above S3 was 2.5 msec (S.D. 0.32). CMCT to L1 (TMCT minus MCT to L1) was 13.8 msec (S.D. 1.13) and to S3 (TMCT minus MEPuL) it was 16.9 msec (S.D. 1.67). This method allows us to locate spinal dysfunction more precisely and also improves diagnosis of a possible neuropathy of the pudendal nerve.

Adult↗

Synaptic shot noise and conductance fluctuations affect the membrane voltage with equal significance.

The subthreshold membrane voltage of a neuron in active cortical tissue is a fluctuating quantity with a distribution that reflects the firing statistics of the presynaptic population. It was recently found that conductance-based synaptic drive can lead to distributions with a significant skew. Here it is demonstrated that the underlying shot noise caused by Poissonian spike arrival also skews the membrane distribution, but in the opposite sense. Using a perturbative method, we analyze the effects of shot noise on the distribution of synaptic conductances and calculate the consequent voltage distribution. To first order in the perturbation theory, the voltage distribution is a gaussian modulated by a prefactor that captures the skew. The gaussian component is identical to distributions derived using current-based models with an effective membrane time constant. The well-known effective-time-constant approximation can therefore be identified as the leading-order solution to the full conductance-based model. The higher-order modulatory prefactor containing the skew comprises terms due to both shot noise and conductance fluctuations. The diffusion approximation misses these shot-noise effects implying that analytical approaches such as the Fokker-Planck equation or simulation with filtered white noise cannot be used to improve on the gaussian approximation. It is further demonstrated that quantities used for fitting theory to experiment, such as the voltage mean and variance, are robust against these non-Gaussian effects. The effective-time-constant approximation is therefore relevant to experiment and provides a simple analytic base on which other pertinent biological details may be added.

Action Potentials↗

Reticulospinal neurones with axons in the dorsal part of the lateral funiculus of the lumbar segments.

The presence of reticulospinal axons in the dorsal part of the lateral funiculus (DLF) of the lumbar spinal cord segments was tested in chloralose-anaesthetized cats. In the medial part of the reticular formation, 59 units which gave antidromic responses to stimulation of the isolated DLF of segment L1--L3 were observed. The rate of their axonal conduction was 20--120 m/s. 62% of the units generated discharge activity in response to electrical stimulation of the skin of the trunk and/or the limbs. The activating intraspinal pathways were localized in the DLF and the ventral part of the cord. The most effective natural stimulus was tapping. Monosynaptic control from cerebellar pathways was confirmed in 37% of reticulospinal neurones with axones in the DLF. The results showed that reticulospinal axones form part of the dorsal reticulospinal system in the lumbar cord region.

Action Potentials↗

Model of synchronized epileptiform bursts induced by high potassium in CA3 region of rat hippocampal slice. Role of spontaneous EPSPs in initiation.

1. We constructed a computer model of the in vitro CA3 region of the rat hippocampal slice bathed in a high-potassium medium. Our aim was to understand better the mechanisms of initiation of synchronized bursts and the processes that regulate the interburst interval in the experimental system. 2. Our model began with a previously published model of the longitudinal CA3 hippocampal slice. The model contains three interconnected cell populations: 9,000 (excitatory) pyramidal cells; 450 inhibitory cells whose postsynaptic action is somatic and decays quickly, corresponding to chloride-dependent inhibition mediated by gamma-aminobutyric acid (GABA)A channels, and 450 inhibitory cells whose postsynaptic action is dendritic, of delayed onset and long lasting, that corresponds to K-dependent inhibition mediated by GABAB channels. 3. The model was then modified to account for specific features of the high-K experimental system: 1) the pyramidal cells do not generate intrinsic bursts; 2) EIPSP(CI) and EK are both shifted in a depolarizing direction; 3) spontaneous (i.e., not caused by presynaptic firing) excitatory postsynaptic potentials (EPSP)s were included; and 4) a steady current was injected into the pyramidal cells to depolarize them. 4. This model generates synchronized population bursts with interburst intervals of approximately 1.0-1.5 s. Bursts in individual pyramidal cells are preceded by barrages of EPSPs. These results agree with experiment. 5. Our model agrees with the following additional experiments: 1) synchronized bursts are abolished by partial blockade of excitatory synapses; 2) burst frequency is increased by partial blockade of a slow-intrinsic-K conductance; and 3) blockade of chloride-dependent inhibition leads to bursts of longer duration with longer interburst intervals. 6. The basic structural features of this model are similar to, but not identical to, the model of the disinhibited hippocampal slice. Spontaneous EPSPs appear to be critical in the high-K system for initiating, but not for synchronizing, population bursts. The experimental data and simulation results raise interesting questions about the role of spontaneous EPSPs in initiating synchronized discharges in other epileptic systems and on the possible role of spontaneous EPSPs in the normal brain.

Action Potentials↗

Comparison of septo-hippocampal with basalo-cortical projection neurons in the rat: an electrophysiological approach.

The electrophysiological properties of septo-hippocampal (SHNs) and basalo-cortical neurons (BCNs) identified by antidromic stimulation were compared in rats anesthetized with urethane. SHNs and BCNs had comparable conduction velocities (about 2-3 m/s) and relatively high spontaneous firing rates (about 20 impulses/s). In contrast, they differed in their pattern of spontaneous discharge as studied by generating inter-spike interval histograms. Many BCNs had a regular pattern of discharge. Among SHNs, about 40% had a spontaneous rhythmically bursting pattern of discharge, whereas the remaining 60% had a more or less irregular pattern. These results suggest that SHNs represent a more heterogeneous neuronal population than BCNs, and that central cholinergic neurons involved in different systems might also have different properties.

Action Potentials↗

Abolition of spindle oscillations in thalamic neurons disconnected from nucleus reticularis thalami.

The effects of depriving thalamic relay and intralaminar nuclei from their reticularis thalami (RE) inputs were investigated in acute and chronic experiments on cat. In acutely prepared animals, two (frontal and parasagittal) thalamic transections were made; extracellular and intracellular recordings were performed in RE-disconnected thalamic nuclei. In chronic experiments, the RE nuclear complex was lesioned by means of kainic acid injections; the activity of RE-deprived thalamocortical neurons was extracellularly studied during wakefulness and synchronized sleep. Two features distinguish RE-deprived nuclei from normal thalamic nuclei: absence of spindle-wave rhythmicity and all-burst activity of neurons. The abolition of spindle-related rhythms (sequences of 7- to 14-Hz waves recurring periodically with a rhythm of 0.1-0.2 Hz) in RE-disconnected thalamic nuclei and ipsilateral neocortical areas contrasted with normal spindling rhythmicity in contralateral EEG leads. Spontaneously occurring, rhythmic, long-lasting inhibitory postsynaptic potentials (IPSPs), as observed in intact preparations, were no longer observed in RE-disconnected thalamic neurons. The remaining inhibitory events consisted of short-duration IPSPs. The possibility that RE nucleus is a pacemaker for spindling rhythms, imposing them through inhibitory projections to target thalamic areas, is supported by our concurrent experiments that indicate RE neurons preserve their rhythmicity after disconnection from their major (cortical and thalamic) input sources. RE-deprived thalamocortical neurons exclusively exhibit high-frequency spike bursts whose intrinsic structure is identical to that of intact thalamic relay cells. Instead of the spindle-related sequences of bursts seen in normal animals, the bursts of RE-disconnected thalamocortical neurons are single events, with a dramatic rhythmicity at 1-2 Hz. The presumed mechanism of this rhythmicity is the periodic activation of a low-threshold somatic conductance whose deinactivation is brought about by temporal integration of short-lasting IPSPs. It is known that high-frequency spike bursts of thalamic relay neurons result from hyperpolarization of cell membrane. We blocked the underlying inhibitory events by bicuculline and reversibly changed the all-burst activity of RE-disconnected neurons into a tonic mode. Since the only activity of RE-deprived thalamocortical neurons consists of burst discharges, we hypothesize that local-circuit GABAergic neurons are released from inhibition after RE disconnection or lesion.

Action Potentials↗

Effects of glutamate, aspartate, and two-presumed antagonists on feline rubrospinal neurones.

The actions of dicarboxyl amino acids (GLUT, ASP, DLH) and of presumed amino acid antagonists (GDEE, HA 966) were studied in rubrospinal neurones with microelectrophoretic techniques. ASP and GLUT depolarized reversibly the cell membrane and increased its conductance. ASP had slightly stronger actions than GLUT. DLH had strong depolarizing actions without a clearcut change in membrane conductance; this may be due to the fact that DLH effects do not involve synaptic receptors. A specific action as antagonists for GLUT could not be shown for GDEE or HA 966. HA 966 effects were often accompanied by apparent postsynaptic actions. GDEE antagonized DLH effects sometimes even stronger than GLUT effects. The effects of GLUT and ASP are in principal agreement with a function as excitatory transmitters. The demonstration of a role as transmitter substances in excitatory (e.g. corticorubral or interpositorubral) pathways, however, still awaits the specific pharmacological antagonist.

Animals↗

Estrogen decreases the responsiveness of subfornical organ neurons projecting to the hypothalamic paraventricular nucleus to angiotensin II in female rats.

Extracellular single-unit activity was recorded from subfornical organ (SFO) neurons antidromically identified as projecting to the hypothalamic paraventricular nucleus (PVN) in urethane-anesthetized ovariectomized female rats that were treated with either propylene glycol (PG) vehicle or estradiol benzoate (EB). No significant differences were observed between the PG- and EB-treated rats in the latency, conduction velocity, or threshold of antidromic activation. The mean spontaneous firing rate was significantly lower and the refractory period was significantly longer in the EB-treated rats. In the identified units that were activated by angiotensin II (ANG II) applied iontophoretically, the amount of excitatory response to intracarotid administration of ANG II was much greater in the PG-treated than in the EB-treated rats. These results suggest that estrogen may decrease the responsiveness of SFO neurons projecting to the PVN to circulating ANG II.

Action Potentials↗

[Effect of tranquilizers on impulse conduction in the afferent pathways of visceral nerves].

Experiments on pyrolaxon-immobilized cats evidence that diazepam produces depression of evoked potentials in the specific, nonspecific and associative brain structures upon an electric stimulation of the visceral and somatic nerves, and also with accoustic and photostimulation; Meprotan (meprobamate) in doses of 40-100 mg/kg neither changes nor increases, and in doses of 100-150 mg/kg, reduces the amplitude of evoked potentials and at the sme time forces down the arterial pressure. Amizyl (benactyzine) inhibits the potentials evoked by stimulation of the vagus. The amplitude of responses arising on stimulation of the inferior cardiac, celiac and sciatic nerves, and also with acoustic and photostimulation neither changes nor increases.

Animals↗

Analysis of motor pathway involvement in konzo using transcranial electrical and magnetic stimulation.

To elucidate the involvement of motor pathways in konzo, 21 konzo subjects (mean age 22 years) underwent transcranial electrical stimulation (TES) in 1998. Fourteen konzo subjects (mean age 21 years) underwent transcranial magnetic stimulation (TMS) in 2000. Three subjects underwent both TES and TMS. Motor evoked potentials (MEPs) were recorded in the abductor pollicis brevis (APB) muscle with TES, and in the abductor digiti minimi (ADM) and tibialis anterior (TA) muscles with TMS. APB-MEPs were normal in 2 of 21 subjects and absent in 9; central conduction time (CCT) was prolonged in 10. Resting ADM-MEPs were absent in 9 of 14 subjects with clinically preserved upper limbs. Among these nine, seven subjects responded after facilitation. Most subjects (13 of 14) failed to show TA-MEPs. Of the subjects who underwent both types of stimulation, one had normal TES-MEP but abnormal ADM-MEP with TMS. These findings suggest involvement of both corticomotoneurons and motor descending pathways in konzo.

Adolescent↗

Variable channel expression in identified single and electrically coupled neurons in different animals.

It is often assumed that all neurons of the same cell type have identical intrinsic properties, both within an animal and between animals. We exploited the large size and small number of unambiguously identifiable neurons in the crab stomatogastric ganglion to test this assumption at the level of channel mRNA expression and membrane currents (measured in voltage-clamp experiments). In lateral pyloric (LP) neurons, we saw strong correlations between measured current and the abundance of Shal and BK-KCa mRNAs (encoding the Shal-family voltage-gated potassium channel and large-conductance calcium-activated potassium channel, respectively). We also saw two- to fourfold interanimal variability for three potassium currents and their mRNA expression. Measurements of channel expression in the two electrically coupled pyloric dilator (PD) neurons showed significant interanimal variability, but copy numbers for IH (encoding the hyperpolarization-activated, inward-current channel) and Shal mRNA in the two PD neurons from the same crab were similar, suggesting that the regulation of some currents may be shared in electrically coupled neurons.

Action Potentials↗