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Electrophysiological analysis of pathways connecting the medial preoptic area with the mesencephalic central grey matter in rats.

1. An electrophysiological study of ascending and descending connexions between the dorsal raphe region of the mesencephalic periaqueductal grey matter and the medial preoptic area has been performed in dioestrous female rats anaesthetized with urethane. 2. Extracellular action potentials recorded from 208 neurones in the medial preoptic area were analysed for a change in excitability following stimulation of the periaqueductal grey matter. 174 neurones were also tested for changes in excitability following stimulation of the mediobasal hypothalamus. 3. Stimulation of the periaqueductal grey matter at 1 Hz was rarely effective, but short trains of pulses (three at 100 Hz) usually caused an initial inhibition (62.5% of 208) of both projection identified and adjacent neurones of the medial preoptic area, at latencies of 5--90 msec (mean 34.1 +/- 1.4 msec). Inhibition following stimulation of the mediobasal hypothalamus occurred less frequently (34%) and at shorter latency (mean 12.0 +/- 1.8 msec; n = 48). 4. Less frequently (10.6%) periaqueductal grey matter stimulation caused an initial excitation of preoptic neurones at latencies of 15--180 msec, (mean 35.3 +/- 7.2). Initial excitation following mediobasal hypothalamus stimulation was stronger, occurred more frequently (29%) and at shorter latencies (range 3--60 msec, mean 13.1 +/- 1.5). Following such initial excitation, inhibition of spontaneous or ionophoretically evoked activity occurred more frequently following mediobasal hypothalamic stimulation, than after periaqueductal grey matter stimulation. 5. Twenty-four neurones displayed antidromic invasion following periaqueductal grey matter stimulation. Latencies for invasion ranged from 13 to 50 msec (mean 25.5 +/- 2.0 msec) and are suggestive of an unmyelinated projection. Occasionally an abrupt decrease in latency followed an increase in stimulus intensity. Antidromic invasion from mediobasal hypothalamus was characterized by a shorter latency (mean 12.5 +/- 0.7 msec; n = 43). A period of reduced excitability lasting 40--100 msec followed antidromic invasion from either site. 6. Antidromic responses to paired mediobasal hypothalamic or periaqueductal grey matter stimuli at 5 msec intervals revealed an increased latency of invasion of the second response, due to the partial refractory period of the neurone. Five cells showed a decreased latency of invasion at stimulus separations of 10--150 msec, interpreted as evidence of a supranormal period. Changes in conduction velocity during the supranormal period may give rise to a variable latency of invasion of spontaneously active cells. 7. These results provide evidence for direct, reciprocal connexions between the midbrain central grey and the medial preoptic area. These circuits may play a role in controlling neuroendocrine and behavioural aspects of reproductive functions.

Action Potentials↗

Dynamic clamp: computer-generated conductances in real neurons.

1. We describe a new method, the dynamic clamp, that uses a computer as an interactive tool to introduce simulated voltage and ligand mediated conductances into real neurons. 2. We simulate a gamma-aminobutyric acid (GABA) response of a cultured stomatogastric ganglion neuron to illustrate that the dynamic clamp effectively introduces a conductance into the target neuron. 3. To demonstrate an artificial voltage-dependent conductance, we simulate the action of a voltage-dependent proctolin response on a neuron in the intact stomatogastric ganglion. We show that shifts in the activation curve and the maximal conductance of the response produce different effects on the target neuron. 4. The dynamic clamp is used to construct reciprocal inhibitory synapses between two stomatogastric ganglion neurons that are not coupled naturally, illustrating that this method can be used to form new networks at will.

Animals↗

Physiologic analysis of central motor pathways--simultaneous recording from multiple relaxed muscles.

The central motor pathways were studied with the technique of percutaneous electrical stimulation of the central nervous system in 40 normal volunteers. There were no significant differences between the right and left sides, or between males and females. A linear correlation between the cortical latency (Lcor) or the spinal latency (Lsp) and body height was observed, however, there was no correlation between the central conduction time (CCT) (Lcor-Lsp) and body height. Consequently, the CCT appears to provide a reliable estimate of the function of central motor pathways. We have established normal values for eight muscles at rest that would be required for localizing a very small intraspinal lesion.

Adult↗

Electrical conductivities of the freshly excised cerebral cortex in epilepsy surgery patients; correlation with pathology, seizure duration, and diffusion tensor imaging.

The electrical conductivities (sigma) of freshly excised neocortex and subcortical white matter were studied in the frequency range of physiological relevance for EEG (5-1005 Hz) in 21 patients (ages 0.67 to 55 years) undergoing epilepsy neurosurgery. Surgical patients were classified as having cortical dysplasia (CD) or non-CD pathologies. Diffusion tensor imaging (DTI) for apparent diffusion coefficient (ADC) and fractional anisotropy (FA) was obtained in 9 patients. Results found that electrical conductivities in freshly excised neocortex vary significantly from patient to patient (sigma = 0.0660-0.156 S/m). Cerebral cortex from CD patients had increased conductivities compared with non-CD cases. In addition, longer seizure durations positively correlated with conductivities for CD tissue, while they negatively correlated for non-CD tissue. DTI ADC eigenvalues inversely correlated with electrical conductivity in CD and non-CD tissue. These results in a small initial cohort indicate that electrical conductivity of freshly excised neocortex from epilepsy surgery patients varies as a consequence of clinical variables, such as underlying pathology and seizure duration, and inversely correlates with DTI ADC values. Understanding how disease affects cortical electrical conductivity and ways to non-invasively measure it, perhaps through DTI, could enhance the ability to localize EEG dipoles and other relevant information in the treatment of epilepsy surgery patients.

Action Potentials↗

Optimization of input patterns and neuronal properties to evoke motor neuron synchronization.

The study used a computational approach to identify combinations of synaptic input timing and strength superimposed on a variety of active dendritic conductances that could evoke similar levels of motor unit synchronization in model motor neurons. Two motor neurons with low recruitment thresholds but different passive properties were modeled using GENESIS software. The timing and strength of synaptic inputs and the density of dendritic ion channels were optimized with a genetic algorithm to produce a set of target discharge times. The target times were taken from experimental recordings made in a human subject and had the synchronization characteristics that are commonly observed in hand muscles. The main finding was that the two parameters with the highest association to output synchrony were the ratio of inward-to-outward ionic conductances (r = 0.344; P = 0.003) and the degree of correlation in inhibitory inputs (r = 0.306; P = 0.009). Variation in the amount of correlation in the excitatory input was not positively correlated with variation in output synchrony. Further, the variability in discharge rate of the model neurons was positively correlated with the density of N -type calcium channels in the dendritic compartments (r = 0.727; P < 0.001 and r = 0.533; P < 0.001 for the two cells). This result suggests that the experimentally observed correlation between discharge variability and synchronization is caused by an increase in fast inward ionic conductances in the dendrites. Given the moderate level of correlation between output synchrony and each of the model parameters, especially at moderate levels of synchrony (E < 0.09 and CIS < 1.0), the results suggest caution in ascribing mechanisms to observations of motor unit synchronization.

Action Potentials↗

Recurrent excitation in neocortical circuits.

The majority of synapses in the mammalian cortex originate from cortical neurons. Indeed, the largest input to cortical cells comes from neighboring excitatory cells. However, most models of cortical development and processing do not reflect the anatomy and physiology of feedback excitation and are restricted to serial feedforward excitation. This report describes how populations of neurons in cat visual cortex can use excitatory feedback, characterized as an effective "network conductance", to amplify their feedforward input signals and demonstrates how neuronal discharge can be kept proportional to stimulus strength despite strong, recurrent connections that threaten to cause runaway excitation. These principles are incorporated into models of cortical direction and orientation selectivity that emphasize the basic design principles of cortical architectures.

Animals↗

Mapping of somato-sensory evoked potentials (SEP): new findings suggesting the role of brain waves as a "temporal analyzer of the stimulus".

For a number of years we have been reporting a relationship between the mid components of the somato-sensory evoked potentials and basic brain waves. Recently we suggested that when the primary spike occurs it elicits a train consisting of beta, alpha, theta and delta single waves, originating at the same point in time and overlapping one with the other. The half periods of each of these waves are equal to the latencies of mid and late SEP components. Thus the latter are in fact the classical brain waves. They are present bilaterally but are of higher amplitude on the parietal region contralateral to the side of the stimulus applied to the median nerve. Presumably at that side the brain wave amplitude is increased by the delayed potentials due to the conduction of some components of the signal travelling in the thin myelinated fibers. Indeed this study revealed the presence of recurrent delayed positive and negative foci in the parietal region contralateral to the side of the stimulus in addition to the late vertex components. Thus brain waves contribute to the temporal analysis of the stimulus.

Adolescent↗

[Centrifugal and centripetal connections of the cat visual cortex].

The responses of the dorsal LGB units to the striate cortex stimulation were examined in cats paralized with d-tubocurarine. Most cells studied were activated antidromically but only 8% demonstrated orthodromic responses. Some units studied intracellularly exhibited antidromic spikes followed by IPSPs, sometimes only IPSP was observed. The conduction velocities of the corticipetal fibres ranged between 28 and 4.3 m/s; three groups of fibres with conduction velocities 28-19, 14-12, 10-9.5 m/s could be separated in them in most cases. Some of the antidromically responding units had different response latencies to different striate areas stumulation, indicating that these units project to the striate cortex by means of a branching axon. Possible mechanisms of cortical influence on the LGB neurons are discussed.

Animals↗

The functional organization of the crayfish lamina ganglionaris. I. Nonspiking monopolar cells.

The light responses of the second order lamina monopolar neurons were examined in the crayfish compound eye. Single cartridge monopolar neurons (M1-M4) exhibited nonspiking hyperpolarizing light responses; for M1, M3 and M4 the transient 'on' response operated over the same intensity range as the receptor, 3.5 log units. M2 operated in a much narrower intensity range (1.5 log unit). The 'on' responses were associated with a 19% increase in conductance. The hyperpolarizing 'on' response can be reversed at 18 mV below the resting membrane potential. The half-angular sensitivity width of monopolar cells (in partially dark-adapted eyes) is 15 degrees X 8 degrees (horizontal by vertical). Off axis stimuli elicit attenuated hyperpolarizing responses associated with a diminished conductance increase or depolarizing responses associated with a net decrease in conductance. The latter result is consistent with the presynaptic inhibition of a 'back-ground' transmitter release which normally persists in the dark. Lateral inhibition is elicited from the area immediately surrounding the excitatory field, and it is associated with diminished transient responses and an accelerated decay of the response. Inhibitory stimuli decrease the conductance change associated with the hyperpolarizing response. The surround stimuli can also elicit depolarizing 'off' responses with reversal potentials positive to the membrane resting potential. It is concluded that the rapidly repolarizing monopolar cell response is modulated by both pre- and postsynaptic inhibitory mechanisms. A compartment model indicates that signal attenuation along a 500 microns length of monopolar cell axon is 22-34%. Simulation of steady-state signal transmission suggests that passive (decremental) conduction is sufficient to convey 66 to 78% of the monopolar cell signal from lamina to medulla. The current-voltage relation in current clamp is linear over the physiological operating range, and there is no evidence for rectification. Hyperpolarization of single monopolar cells (M1-M4) provides a polysynaptic excitatory signal to the medullary sustaining fibers.

Animals↗

Triple projections of neurones located in S1 and S2 segments of the cat spinal cord to the C6 segment, the cerebellum and the reticular formation.

Electrophysiological investigation of neurones in sacral segments of the spinal cord was performed in alpha-chloralose-anaesthetized cats in order to establish whether at least some ascending tract neurones could diverge to three different centres located in the brainstem, the cerebellum or the spinal cord. Recordings of antidromic action potentials from cells in S1 and S2 segments were taken following stimulation of the contralateral gigantocellular nucleus, contralateral restiform body and ipsi- and contralateral grey matter of the C6 spinal segment. Antidromic responses allowed identification of several types of neurones that differed in their pattern of supraspinal or propriospinal projections. In eighteen out of a total of sixty-three neurones triple projections to all the above structures were found. In the majority of cells investigated their axons divided into two branches ascending both ipsi- and contralaterally in the lateral funiculi of the spinal cord. Their cell bodies were distributed in laminae VII-VIII except for a minor group of neurones that projected to the C6 segment only, which were located in laminae V-VI. The latter group also displayed lower values of axonal conduction velocities. Comparison of conduction velocities in proximal and distal parts of axons revealed significant slowing in most, raising the possibility that additional collaterals were present to other spinal or supraspinal centres. Dual and triple projections from most cells in this study suggest that such a divergence may be a more common feature of ascending tract neurones than has been reported before.

Action Potentials↗

Responses of spinocervical tract neurones to noxious stimulation of the skin.

1. Activity of single spinocervical tract neurones has been recorded in the lumbar spinal cord of chloralose anaesthetized or decerebrated cats. Reversible spinalization was produced by cold block at L3. Sensitivity of these neurones to noxious stimulation was studied by heating their cutaneous receptive fields above 40-45 degrees C. 2. Most of the units were located in lamina IV of the dorsal horn and had their receptive fields in the ipsilateral foot. All but one of the studied neurones were excited by moving hairs or by gentle mechanical stimulation of the skin. 3. Eighty-four % of the units were affected by noxious stimuli and three kinds of response were obtained: (i) 61% were excited (E-cells) by noxious heat; (ii) 19% were inhibited (I-cells); and (iii) 19% gave a mixed response reversing from excitatory to inhibitory (EI-cells). 4. E-cells had axons with a wider range of conduction velocities than the rest and also received the strongest descending inhibition from supraspinal structures. 5. The recording sites of EI-cells were located in the medial third of the dorsal horn whereas E- and I-cells were distributed over the full width of the dorsal horn. 6. The possible role of the spinocervical tract in nociception is discussed.

Animals↗

Low voltage bifocal electrical stimulation of the motor cortex.

Currently, non-invasive cerebral motor area stimulation is performed by magnetic or high voltage bifocal electrical stimulation. These techniques require non-conventional stimulators. The present study, performed on 28 normal subjects between 18 and 73 years of age, was designed to standardize a method of bifocal stimulation of motor cortex which uses low voltage conventional stimulators and therefore can be routinely used in electrophysiological laboratories. The hand motor area was stimulated by surface electrodes applied in Cz (cathode) and 8 cm lateral on the bimetal line (anode). Under the electrodes infiltration with Xylocaine 2% was made. Duration and intensity of the rectangular pulses were 150 microseconds and 200-250 Volts, respectively. The motor evoked potential (MEP) was recorded from opponens pollicis muscle by concentric needle electrodes and a slight voluntary contraction was made to facilitate the motor response. MEP latency and central motor conduction time (CMCT) were calculated for both sides. A significant relation with age and height in normal subjects was found only for the MEP latency. We computed also the equations expressing the normal variability between the sides of MEP latency and of CMCT.

Adolescent↗

Somatosensory evoked potentials and central motor pathways conduction after magnetic stimulation of the brain in diabetes.

Somatosensory evoked potentials (SEPs) on stimulating median and posterior tibial nerves, and central and spinal conduction time of the motor pathways calculated by means of magnetic stimulation of the cortex were valuated in diabetic patients. The latencies L1-Cortex and L1-C7 were significantly larger in 54 diabetics than in controls. An increment in L1-C7 interval was found in 17 patients, and the latency L1-Cortex was increased in 20. No patients showed increase in C7-Cortex interval. The increased latency L1-C7 reflects a delayed conduction along afferent spinal pathways in some patients with diabetes in contrast with the normal C7-Cortex supraspinal segment. The central and spinal conduction time after magnetic stimulation of the cortex were normal in 14 out of 15 tested diabetics suggesting that central motor pathways were spared. These results are consistent with the existence of a central-peripheral sensory axonopathy in some diabetics.

Adolescent↗

Magnetic transcranial brain stimulation: painless evaluation of central motor pathways. Normal values and clinical application in spinal cord diagnostics: upper extremities.

Painless transcranial magnetic stimulation has been performed on 53 healthy adults in order to obtain normal values of central motor pathway conduction times to cervical segments innervating upper limb muscles. Central motor latency was 5.1 msec when recording from the biceps brachii and 5.2 msec when recording from the abductor pollicis brevis or abductor digiti minimi muscles. The plexus motor latency as the conduction time between the cervical motor root and the proximal nerve trunks in the axillary region was 2.2 msec and 2.6 msec when recorded from the abductor pollicis brevis and abductor digiti minimi muscles, respectively. Conduction times higher than mean latency + 2 standard deviation may indicate a pathologic conduction slowing. Magnetic stimulation of the motor system is a new painless neurophysiologic technique enabling examination of the central motor pathways in awake subjects. With respect to spinal cord diagnostics, this method is useful in conditions such as compression of the spinal cord or of the motor root in the intervertebral foramen or canal.

Adult↗

GABA-mediated synaptic inhibition of projection neurons in the antennal lobes of the sphinx moth, Manduca sexta.

Responses of neurons in the antennal lobe (AL) of the moth Manduca sexta to stimulation of the ipsilateral antenna by odors consist of excitatory and inhibitory synaptic potentials. Stimulation of primary afferent fibers by electrical shock of the antennal nerve causes a characteristic IPSP-EPSP synaptic response in AL projection neurons. The IPSP in projection neurons reverses below the resting potential, is sensitive to changes in external and internal chloride concentration, and thus is apparently mediated by an increase in chloride conductance. The IPSP is reversibly blocked by 100 microM picrotoxin or bicuculline. Many AL neurons respond to application of GABA with a strong hyperpolarization and an inhibition of spontaneous spiking activity. GABA responses are associated with an increase in neuronal input conductance and a reversal potential below the resting potential. Application of GABA blocks inhibitory synaptic inputs and reduces or blocks excitatory inputs. EPSPs can be protected from depression by application of GABA. Muscimol, a GABA analog that mimics GABA responses at GABAA receptors but not at GABAB receptors in the vertebrate CNS, inhibits many AL neurons in the moth.

Animals↗

Cyclic AMP cascade mediates the inhibitory odor response of isolated toad olfactory receptor neurons.

Odor stimulation may excite or inhibit olfactory receptor neurons (ORNs). It is well established that the excitatory response involves a cyclic AMP (cAMP) transduction mechanism that activates a nonselective cationic cyclic nucleotide-gated (CNG) conductance, accompanied by the activation of a Ca2+-dependent Cl(-) conductance, both causing a depolarizing receptor potential. In contrast, odor inhibition is attributed to a hyperpolarizing receptor potential. It has been proposed that a Ca2+-dependent K+ (K(Ca)) conductance plays a key role in odor inhibition, both in toad and rat isolated olfactory neurons. The mechanism underlying odor inhibition has remained elusive. We assessed its study using various pharmacological agents and caged compounds for cAMP, Ca2+, and inositol 1,4,5-triphosphate (InsP3) on isolated toad ORNs. The odor-triggered K(Ca) current was reduced on exposing the cell either to the CNG channel blocker LY83583 (20 microM) or to the adenylyl cyclase inhibitor SQ22536 (100 microM). Photorelease of caged Ca2+ activated a Cl- current sensitive to niflumic acid (10 microM) and a K+ current blockable by charybdotoxin (20 nM) and iberiotoxin (20 nM). In contrast, photoreleased Ca2+ had no effect on cells missing their cilia, indicating that these conductances are confined to the cilia. Photorelease of cAMP induced a charybdotoxin-sensitive K+ current in intact ORNs. Photorelease of InsP3 did not increase the membrane conductance of olfactory neurons, arguing against a direct role of InsP3 in chemotransduction. We conclude that a cAMP cascade mediates the activation of the ciliary Ca2+-dependent K+ current and that the Ca2+ ions that activate the inhibitory current enter the cilia through CNG channels.

Adenine↗

[Rubrofugal influences on the spike activity of neurons of the medial reticulo-spinal tract].

Synaptic influences from the red nucleus on the activity of the medial reticulo-spinal tract fibres were studied by microelectrode recording in throacic spinal cord of an anesthetized cat. It is found that the red nucleus establishes monosynaptic connections with many pontine and medullary reticulo-spinal neurons with fast (60-105 m/s) and moderate conducting (45-60 m/s) axons. Background activity of these fibres (characterized by grouping of impulses) is accelerated by repetitive stimulation of the red nucleus. Most neurons with slow conducting axons (10-45 m/s) are polysynaptically excited by the red nucleus stimulation, but their background activity (with uniform distribution of impulses) is depressed. Such rubro-reticular influences were also observed in cats with preliminary destroyed tectal and interstitial structures. Some functional aspects of the rubro-reticulo-spinal system are discussed.

Animals↗

[Blink reflex and jaw reflex in neurinoma of the acoustic and trigeminal nerves (author's transl)].

The blink reflex was studied in four patients with neurinoma of the acoustic nerve and in two patients with trigeminal neurinoma. It was abnormal in all cases except in one neurinoma of the acoustic nerve inside the canal. The jaw reflex, studied in four cases, showed unilateral impairment in two cases of trigeminal neurinoma and one case of acoustic neurinoma; it was normal in the case of acoustic neurinoma in the canal. The blink reflex and jaw reflex merit inclusion among the further tests conducted in cases of suspected neurinoma of the trigeminal or acoustic nerves. However, they are of less interest than oto-vestibular tets in the early diagnosis of neurinoma of the eighth nerve. These techniques deserve a place of choice in investigations of atypical facial neuralgia in general and suspected neurinoma of the trigeminal in particular.

Adult↗