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The neuronal organization of the rat subfornical organ in vitro and a test of the osmo- and morphine-receptor hypotheses.

1. Extracellular action potentials (units) were recorded from rat subfornical organ explants in vitro in response to addition of angiotensin II (AII) or carbamyl-choline (carbachol) or serotonin (5-HT) to the superfusion solution. The frequency recorded was dose dependent over a wide range (AII, 0.05--5 nM; carbachol, 2.7--2700 nM; 5-HT, 1--100 nM). Appropriate antagonists, sarc1-ala2 angiotensin (saralasin) for AII, atropine sulphate for carbachol and methysergide maleate for 5-HT, blocked these excitations. The effects were reversible except for that of atropine. 2. Two populations of AII-excited units were found. A superficial population lying between 15 and 45 microns from the ependymal surface was blocked only by saralasin and another population lying more than 55 microns below the ependymal surface could be blocked by atropine as well as saralasin. Carbachol-evoked units generally lay below 45 microns, and 5-HT-evoked units were scattered evenly over the subfornical organ. It is suggested that superficial AII-excited neurones have a cholinergic excitatory synapse with the deeper carbachol-excited neurones. 3. No evidence was found for the hypothesis that neurones of the subfornical organ are excited by morphine or by changes in extracellular osmotic pressure. 4. All types of drug-excited unit, both superficial (15--55 microns) and deep (below 55 microns), could be driven polysynaptically from the body or columns of the fornix. Units driven antidromically or antidromically and synaptically were almost all more than 55 microns from the surface. 5-HT-evoked units were driven antidromically only by stimulation of the columns of the fornix. AII- and carbachol-evoked units could be driven antidromically or antidromically and synaptically by stimulation of the body or the columns of the fornix. It is suggested that AII units driven antidromically are actually carbachol-sensitive neurones driven by the more superficial AII-sensitive cells. 5. A model of the neuronal organization of the subfornical organ is suggested in which AII-sensitive neurones lying superficially are excited by substances borne by blood or cerebrospinal fluid and synapse with deeper carbachol-sensitive neurones. The axons of these deep neurones pass out of the subfornical organ in the columns and body of the fornix. Afferent fibres from the body and columns of the fornix polysynaptically excite both superficial and deep neurones. A recurrent inhibitory circuit is suggested on the output path.

Action Potentials↗

Autogenetic inhibition of motoneurones by impulses in group Ia muscle spindle afferents.

1. Inhibitory post-synaptic potentials evoked by adequate stimulation of group Ia muscle spindle afferents of homonymous and synergistic muscles and by selective electrical stimulation of tendon organ afferents were analysed in motoneurones of triceps surae and plantaris. 2. Selective activation of Ia afferents was verified to occur with brief stretches of triceps surae and plantaris 35 micrometer or less in amplitude with an initial muscle tension of 5 N; stretches of 30--35 micrometer were estimated to activate 80--90% of Ia afferents in these muscles. Under the same conditions the lowest thresholds for group Ib tendon organ afferents were about 40 micrometer. 3. Stretches less than or equal to 30 micrometer evoked i.p.s.p.s in 80% of triceps surae and plantaris motoneurones; lowest thresholds for evoking i.p.s.p.s wef triceps surae and plantaris motoneurones; lowest thresholds for evoking i.p.s.p.s were 10 micrometer or less. However, such low thresholds for stretch-evoked i.p.s.p.s, lower than the thresholds for activation of Ib afferents, were found mainly in spinalized, unanaesthetized (after decerebration) or lightly anaesthetized animals. The latencies of these i.p.s.p.s indicated disynaptic and trisynaptic coupling between Ia afferents and motoneurones. The i.p.s.p.s were evoked (i) from the homonymous and synergistic muscles stretched together, (ii) from the homonymous muscles alone and (iii) from the synergistic muscles alone. 4. Control experiments showed that i.p.s.p.s could be evoked by stretches sub-threshold for discharging motoneurones, thus showing that those i.p.s.p.s were not mediated by Renshaw cells. The stretch-evoked i.p.s.p.s disappeared after sectioning the nerves from the corresponding muscles, further excluding their mediation by afferents other than group Ia afferents from thf stretched muscle. 5. In order to selectively activate tendon organ afferents, thresholds for excitation of Ia afferents by electrical stimuli were increased to a level above the threshold for Ib afferents by prolonged muscle vibration (Coppin, Jack & MacLennan, 1970). I.p.s.p.s evoked by stimuli near threshold for Ib afferents appeared with latencies indicating disynaptic coupling. Later (trisynaptic) components of Ib i.p.s.p.s required somewhat stronger stimuli. 6. Amplitudes of Ia i.p.s.p.s evoked by muscle stretches activating about 80% of muscle spindle afferents were compared with amplitudes of Ib i.p.s.p.s due to less than 50% of tendon organ afferents of the same muscles. The Ia i.p.s.p.s were much smaller (16--35%) than the Ib i.p.s.p.s. The amplitudes of such Ia and Ib i.p.s.p.s constituted about 10 and 25--66%, respectively, of the maximal i.p.s.p.s evoked by electrical stimulation of all group I afferents. 7. We conclude that inhibition of motoneurones may be evoked from Ia muscle spindle afferents from homonymous and synergistic muscles as well as from Ib tendon organ afferents...

Animals↗

Segmental and descending control of the external urethral and anal sphincters in the cat.

1. The present work concerns the contribution of the somatic central nervous system to two viscero-somatic reflexes, micturition and defecation. Descending and segmental actions and properties of the motoneurones innervating the striated external urethral and external anal sphincters were studied with intracellular recording in male cats, under chloralose anaesthesia. 2. Motoneurones innervating the external urethral and external anal sphincters were intermingled and most strongly concentrated in the lateral part of the ventral horn in the S2 segment of the spinal cord. 3. Stimulation of the S1 to S3 ipsilateral dorsal roots or of the homonymous pudendal nerve branches showed that less than half of the sphincter motoneurons receive monosynaptic excitatory connexions from low threshold afferents. 4. The after-hyperpolarization recorded in the external urethral and external anal sphincter motoneurones was relatively short lasting, not long lasting as would have been expected for motoneurones innervating slow-twitch, tonic type muscles. 5. There was no evidence for recurrent inhibition in pudendal motoneurones innervating the external urethral and external anal sphincters. 6. Descending excitation and inhibition to the sphincter motoneurones originated in the nucleus reticularis gigantocellularis of the medullary reticular formation. The descending reticulospinal actions are comparable to those observed in hind limb motoneurones. 7. It is suggested that the segmental reflex connexions play a role in controlling bladder and rectal continence. The descending actions studied also modulate the segmental reflex actions and may provide voluntary control of the sphincter muscles.

Anal Canal↗

The reflex responses of single motor units in human first dorsal interosseous muscle following cutaneous afferent stimulation.

1. Changes in the probability of firing of motor units active during voluntary muscle contraction have been studied in human first dorsal interosseous muscle in response to cutaneous afferent stimulation. 2. Electrical stimulation of the digital nerves of the index finger produces a reflex response consisting of three phases, early excitation followed by inhibition followed by late excitation. 3. Motor units recruited at low levels of voluntary contraction strength had larger early inhibitory and larger late excitatory responses than those recruited at higher levels of force. 4. Taking together the size of the short latency excitatory and inhibitory responses, units recruited at low levels of voluntary contraction strength and with slow twitch contraction times had predominantly inhibitory responses. In contrast, units in which the short latency excitatory responses predominated had fast twitch contraction times and were recruited at high levels of contraction strength. 5. It is concluded that for the cutaneous reflex pathway there are differences in the balance of excitatory and inhibitory sets of interneurones impinging on first dorsal interosseous motoneurones which are related to the kind of muscle unit innervated.

Action Potentials↗

The course of post-ganglionic sympathetic fibres distributed with the trigeminal nerve in the cat.

1. The course of post-ganglionic sympathetic fibres to the jaws, face and eye was investigated in cats by observing the effects of nerve sections on responses evoked by stimulation of the cervical sympathetic trunk. 2. Sympathetic fibres were present in the infraorbital and inferior alveolar nerves. From the superior cervical ganglion, all of these fibres travelled in the internal carotid nerve and all but a few passed through the foramen lacerum and joined the trigeminal nerve at its ganglion. 3. Compound action potentials were recorded from sympathetic fibres in six out of twenty-seven teeth. These fibres followed the route described above. 4. Sympathetic fibres to the pupil and levator palpebrae superioris passed from the internal carotid nerve to the eye via the foramen lacerum and the superior orbital fissure. Some fibres causing piloerection in front of the ear travelled by the same route and some travelled with the maxillary division of the trigeminal nerve. 5. Sympathetic fibres to the nictitating membrane followed a similar route to those supplying the pupil except that they entered the cranial vault through the pterygoid foramen. 6. The secretomotor fibres to the submandibular salivary gland and some vasoconstrictor fibres to the lip did not travel with the internal carotid nerve or major branches of the trigeminal nerve.

Action Potentials↗

Excitation and inhibition of cardiac vagal motoneurones by electrical stimulation of the carotid sinus nerve.

1. The carotid sinus nerve was electrically stimulated in dogs anaesthetized with chloralose. Stimuli (1 ms, 1-10 V, less than or equal to 1 Hz) evoked responses in single cardiac efferent fibres dissected from the cervical part of the vagus nerve. The mean latencies of these responses varied, from fibre to fibre, between 30 and 120 ms. 2. Stimuli given during the expiratory phase of the respiratory cycle evoked vagal responses with a shorter latency than similar stimuli given only during the inspiratory phase of the respiratory cycle. 3. Following the vagal response to carotid sinus nerve stimulation a period of inhibition of vagal activity, lasting 100-150 ms, occurred. Refractoriness of the responding vagal motoneurone following an action potential could not account for this post-excitatory depression. 4. The inhibitory effects of electrical stimulation of the carotid sinus nerve were further studied by applying pairs of similar electrical stimuli to the carotid sinus nerve. The second stimulus of a pair had to be given 80-100 ms after the first to evoke a second response. 5. Trains of electrical stimuli (30-100 Hz) were also studied. At low frequencies the inhibitory effect of successive stimuli on vagal responses became less marked, but at higher frequencies only the first and last stimulus of the train reliably evoked responses. For trains of stimuli at both low and high frequencies, the last stimulus of the train evoked a vagal response, which was succeeded by a period of inhibition of vagal firing: this inhibition was then followed by further excitation before vagal discharge returned to resting levels.

Animals↗

Patterns of activity evoked in cerebellar interpositus nuclear neurones by natural somatosensory stimuli in awake cats.

1. Stable extracellular unitary recordings were made from 138 cerebellar interpositus nuclear neurones (IPNs) in awake cats. Mean background discharge, in animals in a state of relaxed wakefulness and in the absence of overt movement, was 41.0+/-2.6 impulses/sec (mean+/-s.e.m).2. Animals were trained to accept a variety of sensory testing procedures without producing detectable motor reactions. Mechanical taps (1 mm amplitude; 20 msec overall duration) applied to the main pads or dorsal surfaces of the forepaws and/or hind paws modified discharge in forty-eight of 110 IPNs tested. Response patterns to taps generally comprised one or more of three basic components, namely: short-latency excitation, e(1), at onset latencies of 13.0+/-0.9 msec (mean+/-s.e.m.) for ipsilateral forepaw (iF) and 17.0+/-0.7 msec for ipsilateral hind paw (iH); a period of reduced discharge, at latencies 25.6+/-2.6 msec for iF and 32.3+/-2.1 msec for iH; a delayed acceleration of discharge, e(2), at latencies 47.4+/-4.6 msec for iF and 46.4+/-4.1 msec for iH. The component e(1) was the most common (present in 80% of responses) and e(2) the least common (present in 18% of responses).3. The majority (> 70%) of responses of IPNs to tap stimulation of the paws comprised net excitation.4. Convergence of tap-evoked sensory input from iF and iH on to individual IPNs was evident in eight of the thirty-five units tested with stimulation of both afferent sites.5. Approximately one third of IPNs so tested were sensitive to passive manipulation of limb joints in the quiet, awake cat. Sixteen of the forty-three IPNs so tested responded to displacement of the ipsilateral wrist and/or elbow joints and three of ten IPNs so tested responded to movement of contralateral forepaw joints. Corresponding proportions of IPNs responding to passive ankle and/or knee joint displacements were sixteen of thirty-six units tested and three of three units tested for ipsilateral and contralateral hind paws respectively. Convergence of input generated by manipulation of iF and iH joints on to individual IPNs was apparent in only three of twenty-four units tested at each site.6. Tactile stimulation (brushing fur, gentle pressure on the skin) of iF influenced discharge in twelve of thirty-seven IPNs tested and comparable iH-related cutaneous sensory fields were found for fourteen of twenty-eight IPNs tested.7. The modulations of discharge of IPNs associated with active movements of the stimulated limb were usually far more pronounced than those elicited by somatosensory stimulation in the quiet, relaxed animal.8. Responses of IPNs to natural somatosensory stimulation in the awake cat are compared with those previously described for anaesthetized or decerebrate preparations and with those found for electrical stimulation of cutaneous nerves in awake cats. In general IPN response patterns to precisely timed tap stimulation of the paws in the awake animal closely resembled those that would have been predicted from the earlier studies, although the time course of responses differed in certain respects.

Animals↗

Recurrent inhibition of intercostal motoneurones in the cat.

1. The external and internal intercostal nerves of a single intercostal space were stimulated in anaesthetized paralysed cats with dorsal roots cut in the corresponding spinal cord segment. 2. Extracellular recording in the ventral horn revealed single units which fired short high frequency bursts of spikes at short latency to stimulation of either or both of the two nerves at stimulus strengths appropriate to the activation of alpha motor axons. These units were deduced to be Renshaw cells. 3. Small (0.1-0.2 mV) hyperpolarizing potentials of duration up to 50 msec were recorded intracellularly in both inspiratory and expiratory motoneurones of the same segment. Latencies and thresholds were appropriate for disynaptic i.p.s.p.s evoked by collaterals of alpha motor axons. 4. The changes in probability of firing following the stimuli were examined for inspiratory alpha motoneurones by constructing post-stimulus histograms of efferent discharges recorded from filaments of the external intercostal nerve of the segment stimulated and from other segments. 5. A period of reduced probability of firing of up to 24 msec duration, corresponding in all respects to disynaptic inhibition from alpha motor axon collaterals, was seen in the segment stimulated and up to three segments distant, though declining in intensity with distance. Either nerve could evoke such inhibition although that evoked from the internal intercostal nerve was stronger, as were the intensities of the Renshaw cell discharges. 6. We conclude that recurrent inhibition, via Renshaw cells which have axons up to 30 mm in length, is present for intercostal motoneurones. Arguments are adduced to show that although the effects from stimulating any one segmental nerve may be relatively weak, the over-all effect resulting from the widely spread projections of the Renshaw cells concerned is an inhibition comparable intensity with that seen in many hind limb motor nuclei.

Action Potentials↗

The maturation of cutaneous reflexes studied in the upper limb in man.

Cutaneous reflex responses have been recorded from forearm flexor and extensor muscles following electrical stimulation of the fingers. Recordings have been made from premature infants, term infants and children between the age of 6 weeks and 11 years. In the new-born, stimulation of the fingers elicits such a powerful reflex that, in general, individual stimuli will evoke a reflex synchronous action potential in both forearm flexor and extensor muscles. Individual stimuli delivered to the fingers also elicit reflex synchronous muscle action potentials in forearm flexor and extensor muscles in patients with clinical signs of upper motor neurone lesion affecting the upper limb; this has not been observed in normal adult subjects. The latency of the reflex response in the term infant is about 18 msec. Comparison of this value with the latency of the tendon jerk for these muscles would indicate a central delay for the cutaneous reflex of about 3 msec. The latencies of the cutaneous reflex and tendon jerk remain constant over the first 5 years of life. The size of the short-latency cutaneous reflex response decreases progressively over the first year of life. In the second year of life stimulation of the fingers produces long- as well as short-latency increases in recorded muscle electrical activity. The maturation of the cutaneous reflex response is discussed in terms of the maturation of function of the corticospinal tract.

Action Potentials↗

Effects of hind limb nerve section on lumbosacral dorsal horn neurones in the cat.

The sciatic and saphenous nerves of one hind limb were sectioned in young adult cats anaesthetized with halothane. Between 19 and 55 days later, under chloralose anaesthesia, dorsal horn neurones in the L6 and L7 segments were recorded and their receptive field properties examined. In seven animals recordings were made from identified spinocervical tract, post-synaptic dorsal column and dorsolateral funicular neurones as well as from neurones that did not project through these pathways. Thirty-one neurones were intracellularly stained with horseradish peroxidase, and fifty-three were recorded extracellularly and located by reference to stained cells. In two animals (both 31 days after nerve section) no attempt was made to identify axonal projections of the dorsal horn neurones in order to avoid any effects of cervical cord search stimuli on the cells' properties, but all isolated extracellularly recorded units were examined. On the side ipsilateral to the nerve sections 143 units were recorded. In all experiments, neurones in the medial three-quarters of the dorsal horn had no discernible cutaneous, mechanosensitive receptive fields between 19 and 55 days after nerve section. There were only two exceptions to this generalization, one neurone being one of the most rostral cells in the sample (in caudal L5) and the other being one of the most caudal cells (in caudal L7). We present evidence to show that neither of these two neurones had inappropriate receptive fields in terms of the somatotopic organization of the dorsal horn. All other neurones with receptive fields on the skin were appropriately located in the somatotopic map laid out in the dorsal horn. There was no evidence for gross anatomical changes in the dendritic trees of dorsal horn neurones following sciatic and saphenous nerve sections. We have been unable to confirm that, following loss of cutaneous receptive fields by peripheral nerve section, dorsal horn neurones in adult cats acquire 'inappropriate' receptive fields. Possible reasons for this are discussed.

Animals↗

Selective block of Y optic nerve fibres in the cat and the occurrence of inhibition in the lateral geniculate nucleus.

A method of selectively blocking the larger nerve fibres in the optic nerve of the cat is described. The optic nerve is compressed between a small balloon and the inside of a small metal cylinder. The block is monitored by stimulating and recording on opposite sides of the blocked region. The t1 (Y) response can be eliminated usually with some loss of the t2 (X) response. Stimulation of the blocked optic nerve initially excites certain cells (r2 or X) in the dorsal lateral geniculate nucleus (d.l.g.n.) but this is followed by an inhibition of both r1 (Y) and r2 (X) cells. This inhibition is similar in time course to that produced by stimulation of t1 fibres, suggesting that the effect may be mediated via a similar mechanism. The effect is present in a preparation in which all t1 fibres have degenerated, removing the possibility that it might have been due to inadvertent stimulation of t1 fibres. Experiments on a small number of r2 (X) d.l.g.n. cells have confirmed the inhibitory effect of stimulation of the smaller optic nerve fibres on X cells.

Action Potentials↗

Relations between spinocervical and post-synaptic dorsal column neurones in the cat.

1. In chloralose-anaesthetized cats single-unit micro-electrode recordings were made at the lumbosacral level either from axons in the dorsolateral funiculus and dorsal columns, identified as belonging to the spinocervical tract (s.c.t.) or post-synaptic dorsal column (p.s.d.c.) pathway respectively, or from neurones in the dorsal horn similarly identified. 2. Attempts were made to show that s.c.t. and p.s.d.c. neurones had axons that bifurcated, so that they sent branches into both the ipsilateral dorsolateral funiculus and the dorsal columns. That is, that some, or all, of the presumed s.c.t. or p.s.d.c. axons were common to both populations. In addition, the effects of stimuli applied to the ipsilateral dorsolateral funiculus at C3 and C1 on the resting discharges of p.s.d.c. neurones were examined in order to determine the effectiveness of the link between the s.c.t. and the p.s.d.c. pathway. 3. Thirty-three s.c.t. units (twenty-six axonal recordings and seven soma-dendritic recordings) and thirty p.s.d.c. units (twenty-four axonal and six soma-dendritic recordings) were examined for bifurcating axons by electrically stimulating the dorsolateral funiculus at C3 and the dorsal columns at C4. None of the p.s.d.c. units could be antidromically activated from the ipsilateral dorsolateral funiculus with stimulus strengths up to 40 V or seventy times threshold for antidromic activation from the dorsal columns. Similarly, twenty s.c.t. units could not be activated antidromically from the dorsal columns at stimulus strengths up to 30 V or thirty times threshold for their antidromic excitation from the dorsolateral funiculus. Thirteen s.c.t. units were antidromically activated from the cervical dorsal columns, eight at seventeen or more times threshold for their activation from the dorsolateral funiculus and five at between two and nine times threshold. All s.c.t. units that were activated antidromically from both the cervical dorsal columns and the dorsolateral funiculus showed similar latencies for the two responses. 4. Twenty-five p.s.d.c. units were examined for the effects of ipsilateral dorsolateral funiculus stimulation on their resting activity. In thirteen, clear evidence of facilitatory effects from C3 were observed, whereas similar results were seen in only six of these units when C1 was stimulated and the effects were less. The facilitation had a latency of 3-16 ms and lasted for 6-22 ms. In all but one of the twenty-five units, stimulation at both C1 and C3 produced profound inhibition of the resting discharge that began at between 8 and 26 ms and lasted for up to 300 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Pulmonary stretch receptor relay neurones of the cat: location and contralateral medullary projections.

1. The activity of pump (p.) cells, second-order neurones in the pulmonary stretch receptor pathway, was recorded extracellularly in the nucleus of the tractus solitarius (n.t.s.) of the decerebrate cat. Their firing was proportional to changes in lung volume but unrelated to the centrally determined respiratory rhythm. A systematic search of the n.t.s. for the location of p. cells was made and an assessment of their efferent projection to the contralateral n.t.s. was determined electrophysiologically by the antidromic mapping technique. 2. P. cells were located around, and in close proximity to, the solitary tract. The two sites of greatest density were ventromedial and dorsolateral to the tract, with lower concentrations found laterally and ventrolaterally. 3. For twelve of the thirty p. cells tested, evidence of a projection to the contralateral n.t.s. was obtained; in seven of these cells, axonal arborizations within the projection area were identified. Almost all the cells that sent axons to the contralateral n.t.s. were located dorsolateral to the tract; there was no evidence that cells in the ventromedial region had contralateral projections. 4. No evidence that R beta neurones project to the contralateral commissural and ventrolateral subnuclei was found. 5. No p. cells projected to the contralateral ventrolateral n.t.s. The site of projection and branching was consistently localized just caudal to the obex and medial to the solitary tract, in the caudal medial, and commissural subnuclei of the n.t.s. This same region has been shown to receive a dense, direct projection from pulmonary rapidly adapting receptors.

Animals↗

Group II-activated lumbosacral interneurones with an ascending projection to midlumbar segments of the cat spinal cord.

1. In anaesthetized cats, single-unit microelectrode recordings were made in the lateral funiculus at L6, from the axons of lumbosacral interneurones discharged by hindlimb group II muscle afferents. 2. The level of the ascending projection of these interneurones was investigated by antidromic activation of their axons in the lateral funiculus from different spinal levels. The majority of units encountered were found to have an ascending projection to at least the L4 level and, of these, most (85%) did not project beyond the L4 or L3 segments of the cord. 3. The axons studied were discharged by group II afferents primarily from knee extensor muscles. Some units were discharged in addition by cutaneous and/or joint afferents. 4. The implications of this ascending projection are discussed.

Animals↗

Corticofugal action on transmission of group I input from the hindlimb to the pericruciate cortex in the cat.

1. In cats anaesthetized with alpha-chloralose, evidence was sought for a corticofugal action on input from muscle group I afferents projecting to the cerebral cortex via the brain stem relay at nucleus Z. 2. Extracellular recordings were made of responses of thirty-four nucleus Z neurones which could be activated by stimuli at group I strength applied to each of a variety of hindlimb muscle nerves. Afferent input to each nucleus Z neurone was restricted to a single muscle. 3. Nucleus Z neurones typically showed a resting discharge which could be increased or decreased by altering the amount of stretch on the muscle which was the source of the afferent input. Ventral root stimulation gave response patterns which showed these neurones to be driven by input from either tendon organs or muscle spindles, but not both. 4. A brief train of focal, cathodal stimuli applied to a discrete region of pericruciate cortex could consistently inhibit the maintained activity evoked by muscle stretch in nucleus Z neurones, or the response evoked by stimulation of the muscle nerve at group I strength. The inhibition was powerful and lasted 50-400 ms. The effective stimulating site corresponded to area 3a, the main cortical receiving area for hindlimb muscle group I input. 5. Since the ascending spinal axons which project to nucleus Z are collaterals of dorsal spinocerebellar tract fibres, it was possible to stimulate the parent axons at their termination in the anterior lobe of the cerebellum. Cortical stimulation was found to have little or no effect on activity in nucleus Z neurones evoked by cerebellar stimulation over conditioning-test intervals in the range 10-200 ms. 6. It is concluded that over the time intervals for which it has been tested, corticofugal inhibitory action appears to be largely operating at the first spinal segmental relay, in Clarke's column. Thus the inhibitory action arising in area 3a of the cerebral cortex will suppress the action of input from hindlimb group I fibres at the level both of the cerebellum and the cerebral cortex.

Animals↗

Afferent inhibition and facilitation of transmission through the spinocervical tract in the anaesthetized cat.

1. Extracellular microelectrode recordings were made from single spinocervical tract (SCT) neurones in the lumbosacral spinal cord of cats anaesthetized with chloralose and paralysed with gallamine triethiodide. 2. Pairs of air-jet stimuli, 60 ms in duration, were used to investigate in-field afferent inhibition in SCT cells. One jet was used to condition the responses to another jet located at a different position within the excitatory receptive field and occurring at times from 100 to 1800 ms later. Fifteen neurones were tested and significant in-field inhibition was observed in all of them. 3. The in-field afferent inhibition was organized spatially in the sense that inhibition was generally strongest when conditioning and testing stimuli were close together and became weaker as they were moved apart. There was also a weak effect due to the strength of the conditioning response; when conditioning produced a strong response, from near the most excitable part of the receptive field, there was often a weak reduction in the test response from distant sites. The inhibitory areas defined in these experiments were generally less than 100 mm in length in units with excitatory receptive fields much longer than this. 4. The in-field afferent inhibition had a time course that lasted from 300 to about 1000 ms. 5. Afferent inhibition was also evoked by applying either air-jet stimuli to hairy skin outside, but close to, the excitatory receptive field or by applying a vibratory stimulus from a piezoelectric transducer (200 Hz) to glabrous skin of the toe pads or the central foot pad. These conditioning stimuli had durations of 20 or 60 ms. For convenience we call this inhibition 'out-of-field' afferent inhibition. 6. Out-of-field afferent inhibition was evoked from both glabrous and hairy skin areas outside the excitatory receptive field. It was common in neurones with receptive fields on the toes and of twenty-eight such neurones tested it was observed in twenty-four. This inhibition had a short latency (usually about 10 ms or less but occasionally up to 30 ms) and lasted for about the duration of the test stimulus (30 or 80 ms when the test stimulus was 20 or 60 ms respectively). It was often followed by a further period of inhibition, with a latency of between 50 and 100 ms and lasting for 60 up to 130 ms. 7. In thirteen SCT neurones more complex effects were seen.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex.

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input-output curve and motor thresholds as global parameters of cortico-spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I-wave) interactions. Measurements were performed during short-term tDCS, which elicits no after-effects, and during other tDCS protocols which do elicit short- and long-lasting after-effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input-output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico-spinal excitability during a short period of stimulation (which does not induce after-effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input-output curve, but not motor thresholds. In contrast, the after-effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I-wave interaction, which is controlled by synaptic activity.

Adult↗

Modelling spinal circuitry involved in locomotor pattern generation: insights from deletions during fictive locomotion.

The mammalian spinal cord contains a locomotor central pattern generator (CPG) that can produce alternating rhythmic activity of flexor and extensor motoneurones in the absence of rhythmic input and proprioceptive feedback. During such fictive locomotor activity in decerebrate cats, spontaneous omissions of activity occur simultaneously in multiple agonist motoneurone pools for a number of cycles. During these 'deletions', antagonist motoneurone pools usually become tonically active but may also continue to be rhythmic. The rhythmic activity that re-emerges following a deletion is often not phase shifted. This suggests that some neuronal mechanism can maintain the locomotor period when motoneurone activity fails. To account for these observations, a simplified computational model of the spinal circuitry has been developed in which the locomotor CPG consists of two levels: a half-centre rhythm generator (RG) and a pattern formation (PF) network, with reciprocal inhibitory interactions between antagonist neural populations at each level. The model represents a network of interacting neural populations with single interneurones and motoneurones described in the Hodgkin-Huxley style. The model reproduces the range of locomotor periods and phase durations observed during real locomotion in adult cats and permits independent control of the level of motoneurone activity and of step cycle timing. By altering the excitability of neural populations within the PF network, the model can reproduce deletions in which motoneurone activity fails but the phase of locomotor oscillations is maintained. The model also suggests criteria for the functional identification of spinal interneurones involved in the mammalian locomotor pattern generation.

Action Potentials↗