Neuronal and synaptic mechanisms of cortical inhibition

The latent periods, amplitude, and duration of IPSPs arising in neurons in different parts of the cat cortex in response to afferent stimuli, stimulation of thalamocortical fibers, and intracortical microstimulation are described. The duration of IPSPs evoked in cortical neurons in response to single afferent stimuli varied from 20 to 250 msec (most common frequency 30–60 msec). During intracortical microstimulation of the auditory cortex, IPSPs with a duration of 5–10 msec also appeared. Barbiturates and chloralose increased the duration of the IPSPs to 300–500 msec. The latent period of 73% of IPSPs arising in auditory cortical neurons in response to stimulation of thalamocortical fibers was 1.2 msec longer than the latent period of monosynaptic EPSPs evoked in the same way. It is concluded from these data that inhibition arising in most neurons of cortical projection areas as a result of the arrival of corresponding afferent impulsation is direct afferent inhibition involving the participation of cortical inhibitory interneurons. A mechanism of recurrent inhibition takes part in the development of inhibition in a certain proportion of neurons. IPSPs arise monosynaptically in 2% of cells. A study of responses of cortical neurons to intracortical microstimulation showed that synaptic delay of IPSPs in these cells is 0.3–0.4 msec. The length of axons of inhibitory neurons in layer IV of the auditory cortex reaches 1.5 mm. The velocity of spread of excitation along these axons is 1.6–2.8 msec (mean 2.2 msec).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 394–403, May–June, 1984.     

Effects of Stimulation of the Periaqueductal Gray and <Emphasis Type="Italic">Locus Coeruleus</Emphasis> on Postsynaptic Reactions of Cat Somatosensory Cortex Neurons Activated by Nociceptors

In cats, we studied the influences of stimulation of the periaqueductal gray (PAG) and locus coeruleus (LC) on postsynaptic processes evoked in neurons of the somatosensory cortex by stimulation of nociceptive (intensive stimulation of the tooth pulp) and non-nociceptive (moderate stimulations of the infraorbital nerve and ventroposteromedial nucleus of the thalamus) afferent inputs. Twelve cells activated exclusively by nociceptors and 16 cells activated by both nociceptive and non-nociceptive influences (hereafter, nociceptive and convergent neurons, respectively) were recorded intracellularly. In neurons of both groups, responses to nociceptive stimulation (of sufficient intensity) looked like an EPSP-spike-IPSP (the latter, of significant duration, up to 200 msec) complex. Electrical stimulation of the PAG (which could itself evoke activation of the cortical neurons under study) resulted in long-term suppression of synaptic responses evoked by excitation of nociceptors (inhibition reached its maximum at a test interval of 600 to 800 msec). We observed a certain parallelism between conditioning influences of PAG activation and effects of systemic injections of morphine. Isolated stimulation of LC by a short high-frequency train of stimuli evoked primary excitatory responses (complex EPSPs) in a part of the examined cortical neurons, while in other cells high-amplitude and long-lasting IPSP (up to 120 msec) were observed. Independently of the type of the primary response to PAG stimulation, the latter resulted in long-term (several seconds) suppression of the responses evoked in cortical cells by stimulation of the nociceptive inputs. The mechanisms of modulatory influences coming from opioidergic and noradrenergic brain systems to somatosensory cortex neurons activated due to excitation of high-threshold (nociceptive) afferent inputs are discussed.Neirofiziologiya/Neurophysiology, Vol. 37, No. 1, pp. 61–73, January–February, 2005.     

Connections of thalamic nucleus lateralis posterior with suprasylvian cortex in cats

Cats were immobilized with D-tubocurarine. Responses of 231 neurons of the thalamic nucleus lateralis posterior to cortical stimulation in areas 5b and 21 of the suprasylvian gyrus were studied. Responses of 34 neurons were antidromic, indicating the existence of a direct projection of this nucleus to the cortical areas studied. This projection was most extensive in area 5b. The long latencies (up to 60 msec) of the antidromic responses of some neurons indicate that axons of certain neurons of thalamic nucleus lateralis posterior conduct excitation very slowly (0.3 m/sec). Orthodromic responses with latencies of 2–3 msec to cortical stimulation point to the presence of direct pathways from cortex to nucleus. The flow of afferent impulses into the nucleus from area 5b is stronger than from area 21. Convergence of impulses from these areas was observed on 44% of neurons of the nucleus. Cortical stimulation of areas 5b and 21 evoked postsynaptic inhibition in most neurons of the nucleus. It is concluded that two-way direct connections exist between nucleus lateralis posterior of the thalamus and the suprasylvian cortex.     

Raphe Stimulation-Evoked Modulation of Postsynaptic Responses by Neurons of the Cat Somatosensory Cortex Activated by Stimulation of Nociceptors

We studied the effects of electrical stimulation of the raphe nuclei (RN) of the cat brain on postsynaptic potentials developing in somatosensory cortex neurons activated by nociceptive influences. Intracellular records were obtained from 15 cells, which were either selectively excited by stimulation of nociceptors (intense electrical stimulation of the dental pulp) or activated by both the above nociceptive and non-nociceptive (moderate stimulations of the infraorbital nerve or thalamic ventroposteromedial nucleus, VPMN) influences. In neurons of both groups, stimulation of both nociceptive afferents and the VPMN evoked complex responses (EPSP–AP–IPSP; IPSPs were 200 to 300 msec long). In some studied cortical neurons, isolated electrical stimulation of the RN (which caused the release of serotonin, 5-HT, in the cortex) resulted in relatively short-latency synaptic excitation, while inhibition was observed in other cells. In the case where stimulation of the RN was used as conditioning influence, such stimulation (independently of the kind of the initial response to RN stimulation) led to long-latency and long-lasting suppression of all components of the synaptic reactions evoked by excitation of nociceptors. The maximum of inhibition was observed at test intervals of 300 to 800 msec. The mechanisms underlying modulatory influences coming from the 5-HT-ergic brainstem system to neurons of the somatosensory cortex, which are activated by excitation of high-threshold (nociceptive) afferent inputs, are discussed.     

Interaction between unit responses of the cat cerebellar cortex during paired stimulation of the forelimbs

Interaction between spike responses of 41 cerebellar cortical neurons to electrical stimulation of the two forelimbs with different intervals between stimuli were studied in cats anesthetized with chloralose and pentobarbital. The responsiveness of neurons with a phasic type of discharge to testing stimulation of the limb was reduced for 300–500 msec or longer after conditioning stimulation of the other limb. Interaction between the responses was less clear in neurons with a tonic type of response. Interaction was absent or was summating in character if the stimuli were applied at the same times. Only if the intertrial intervals were 50–150 msec was regular inhibition of the responses of tonic type to the testing stimulus observed. It is postulated that the nucleus of the inferior olive participates in the interaction between phasic unit responses during simultaneous stimulation of the two limbs or to stimulation separated by short intervals (under 30 msec). With longer intervals between stimuli, interaction between responses of either type is connected with involvement of the lateral reticular nucleus. In the process of interaction competitive relations may develop between responses caused by impulses reaching neurons of the cerebellar cortex along climbing and mossy fibers.     

Unit responses of the first and second somatosensory cortical areas to peripheral,thalamic, and cortical stimulation

Unit responses of the first (SI) somatosensory area of the cortex to stimulation of the second somatosensory area (SII), the ventral posterior thalamic nucleus, and the contralateral forelimb, and also unit responses in SII evoked by stimulation of SI, the ventral posterior thalamic nucleus, and the contralateral forelimb were investigated in experiments on cats immobilized with D-tubocurarine or Myo-Relaxin (succinylcholine). The results showed a substantially higher percentage of neurons in SII than in SI which responded to an afferent stimulus by excitation brought about through two or more synaptic relays in the cortex. In response to cortical stimulation antidromic and orthodromic responses appeared in SI and SII neurons, confirming the presence of two-way cortico-cortical connections. In both SI and SII intracellular recording revealed in most cases PSPs of similar character and intensity, evoked by stimulation of the cortex and nucleus in the same neuron. Latent periods of orthodromic spike responses to stimulation of nucleus and cortex in 50.5% of SI neurons and 37.1% of SII neurons differed by less than 1.0 msec. In 19.6% of SI and 41.4% of SII neurons the latent period of response to cortical stimulation was 1.6–4.7 msec shorter than the latent period of the response evoked in the same neuron by stimulation of the nucleus. It is concluded from these results that impulses from SI play an important role in the afferent activation of SII neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 4, pp. 351–357, July–August, 1976.     

Electrophysiological investigation of conduction of afferent impulses through the medial geniculate body

Extra- and intracellular reactions of 280 neurons of the pars principalis of the medial geniculate body (MGB) and of 408 auditory cortical neurons in area AI to stimulation of the inferior brachium of the midbrain and geniculocortical fibers were studied in cats immobilized with D-tubocurarine. Single electrical stimulation of the inferior brachium was shown to evoke a long and complex neuronal response in MGB in the form of excitation of some and inhibition of other neurons. The initial component of this response lasted 13 msec. Excitation of 72% of neurons participating in the response took place during the first 3 msec after the beginning of stimulation. In the same period 84% of IPSP arose. The inferior brachium was shown to contain a certain number of descending fibers. Some of them are axons of MGB neurons. Many fibers of the inferior brachium reach the auditory cortex without synaptic relay in MGB. Of all cells of MGB excited by stimulation of the inferior brachium monosynaptically, 76% are thalamocortical relay neurons; the rest are interneurons. Of the relay neurons of MGB 90% are excited monosynaptically, the rest by impulses passing through two or three synaptic relays in MGB. During stimulation of the inferior brachium, responses consisting of EPSP-IPSP and primary IPSP are recorded in many neurons of MGB. About 20% of primary IPSP arise monosynaptically, evidently in response to stimulation of inhibitory fibers of the inferior brachium. Most IPSP arise disynaptically, with the participation of an inhibitory interneuron located at the entrance to MGB. Inhibition observed in this case is direct afferent in nature.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 515–523, November–December, 1979.     

Peripheral and Spinal Inputs to Physiologically Identified Thalamic and Nonthalamic Relay Neurons in Cat Cuneate Nucleus

A single-unit population study of the feline cuneate nucleus was carried out to identify principal neuron types, their distribution within the nucleus, pattern of peripheral activation, and receptive field characteristics. Units were also tested for response to isolated dorsal column or dorsolateral funicular electrical stimulation. The nucleus was explored in a uniform pattern, and sample size was optimized by applying the search stimulus shocks to the dorsal spinal cord. Single units were defined as spinal afferents, cuneothalamic-relay (CTR) neurons, and non-cuneothalamic-relay (non-CTR) neurons. The following features were observed: (1) The distribution within the nucleus of specific cell types agreed with cytoarchitectural studies: Spinal afferent fibers were superficial and caudal; 22% of neurons were CTR neurons; CTR neurons were most dense in the middle of the nucleus and were largely separate from non-CTR neurons. (2) Of the 58 neurons tested for response to isolated dorsal column and dorsolateral funicular stimulation, 24% were activated from both tracts. (3) Convergent input from the off-focus periphery (defined as other than the ipsilateral forelimb) was detected in both CTR and non-CTR neurons, most commonly from the contralateral forepaw. Several neurons were activated from three limbs. (4) Thirty-seven percent of units were unresponsive to hair movement, touch, muscle palpation, or movement of joints. Compared to spinal fibers and non-CTR neurons, CTR neurons were most likely to have an identifiable input.     

Electrophysiological investigation of effect of pulvinar stimulation of caudate nucleus neurons that react to visual stimulation

Responses of caudate neurons to electrical stimulation of the afferent input from thepulvinar thalamic nucleus and to visual stimuli of various orientations were studied extracellularly in awake chronic cats. Activation responses dominated among reactions of these neurons. The response latencies have ranged from 4 to 85 msec for units with primary activation and from 20 to 150 msec for inhibited ones. The values are indicative of both rapidly and slowly conducting afferent pathways. A possibility of monosynaptic transmission in thepulvinarcaudate projections is also revealed.Pulvinar stimulation is found to be efficient for a significant (more than 50 percent) number of caudate neurons responding to visual stimuli, including orientation-selective cells. The mode of influences from other structures of the visual system (optic tract, area 17, the Clare-Bishop area) on caudate neurons responding topulvinar stimulation is described. The data are discussed with respect to the possible role of cortical and subcortical projections of the visual system in the creation of sensory specific responses of the caudate nucleus.A. A. Bogomolets Physiology Institute, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 5, pp. 520–529, September–October, 1991.     

Responses of cat cerebellar cortical neurons to stimulation of the caudate nucleus,globus pallidus,and substantia nigra

Stimulation of the head of the caudate nucleus in cats anesthetized with chloralose and pentobarbital evoked spike responses of the Purkinje cells and other cerebellar cortical neurons in the paramedian lobes, lobulus simplex, and the tuber of the vermis. Phasic responses in the form of simple discharges (on account of activation of the neurons through mossy fibers) appeared mainly after a latent period of 5–12 and 14–20 msec; the latent period of responses consisting of complex discharges (on account of activation of Purkinje cells through climbing fibers) was 5–6, 9–22 msec, or more. Depending on the latent period, the spike responses differed in their rhythm of generation. In response to stimulation of the caudate nucleus with a frequency of 4–6/sec recruiting responses were found. An inhibitory pause was an invariable component of the tonic responses. During stimulation of the globus pallidus responses of the same types (phasic and tonic) appeared as during stimulation of the caudate nucleus, but they differed in the distribution of the neurons by latent period of spike responses. The minimal latent period was 4 msec. Recruiting also was observed during repetitive stimulation of the globus pallidus. During stimulation of the substantia nigra Pukinje cells activated by climbing fibers responded. Evoked complex discharges appeared after a stable latent period of 8.5±0.3 msec. Arguments are put forward regarding the role of the substantia nigra, the globus pallidus, nuclei of the inferior olive, and also the thalamic nuclei in the mechanism of caudato-cerebellar oligosynaptic and polysynaptic connections.N. I. Pirogov Medical Institute, Vinnitsa. Translated from Neirofiziologiya, Vol. 10, No. 4, pp. 375–384, July–August, 1978.     

Functional properties distinguishing individual auditory cortical neurons

Responses of 246 auditory cortical neurons to paired and repetitive stimulation of geniculo-cortical fibers were studied in experiments on cats immobilized with tubocurarine. The refractory period (RP) varied from 1 to 200 msec in different neurons. For neurons excited antidromically it varied from 1 to 3 msec. Among neurons excited monosynaptically there were some with a short (1.3–6 msec), medium, (8–16 msec) or long (30–100 msec) refractory period. Most neurons excited polysynaptically had a RP of mean length. RPs 30–200 msec in length were due to inhibition arising in the neuron after conditioning stimulation. In some neurons, after a short (1.5–2.0 msec) initial period of refractoriness there was a temporary (for 2–3 msec) recovery of responsiveness, followed by another period of ineffectiveness of the testing stimulus lasting 30–100 msec. Barbiturates selectively inhibited long-latency unit responses in the auditory cortex and during their action the number of responding neurons with a mean RP decreased sharply. The results demonstrate functional heterogeneity of auditory cortical neurons responding to an incoming volley of afferent impulses.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 236–245, May–June, 1973.     

Monosynaptic inhibitory postsynaptic potentials of cortical neurons

Monopolar intracortical stimulation of the auditory cortex was carried out in cats immobilized with D-tubocurarine. A macroelectrode (tip diameter 100 µ) or a microelectrode (tip diameter 10–15 µ) was used for stimulation. In both cases, besides excitatory responses, primary IPSPs with latent periods of 0.4–1.2 and 1.4–6.0 msec were recorded in cortical neurons close to the point of stimulation. The first group of IPSPs are considered to be generated in response to direct stimulation of bodies or axons of inhibitory cortical neurons, i.e., monosynaptically. The amplitude of these IPSPs varied in different neurons from 3 to 15 mV, and their duration from 4 to 150 msec. Additional later inhibitory responses were superposed on many of them. Of the IPSPs generated in auditory cortical neurons in response to stimulation of geniculocortical fibers 1.5% had a latency of 0.8–1.3 msec. They also are assumed to be monosynaptic. It is concluded that the duration of synaptic delay of IPSPs in cortical neurons and spinal motoneurons is the same, namely 0.3–0.4 msec. Axons of auditory cortical inhibitory neurons may be 1.5 mm long. The velocity of impulse conduction along these axons is 1.6–2.8 m/sec. The genesis of some special features of IPSPs of cortical neurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 7, No. 5, pp. 458–467, September–October, 1975.     

Connections of the second auditory cortical area with the medial geniculate body and the first auditory area

Extra — and intracellular unit responses in area AII to stimulation of geniculocortical fibers and of area AI were studied in cat immobilized with D-tubocurarine. In response to stimulation of geniculocortical fibers, antidromic mono-, di-, and polysynaptic spikes were generated by neurons in area AII. The number of antidromic responses in area AII was about half that found in area AI under the same conditions of stimulation. Most of the orthodromic responses were di- and polysynaptic. Intracellular responses also were recorded in the form of EPSPs, EPSP-IPSPs, and primary IPSPs. Stimulation of area AI evoked responses in the neurons of area AII with latent periods of 0.75–6.0, 6.1–16.0, 18.0–23.0, and 60–100 msec. Removal of the medial geniculate body led to a marked decrease in the number of responses with latent periods of 6.1–16.0 msec. Some neurons of area AII responded by spikes to stimulation of both the geniculocortical fibers and area AI. Comparison of the latent periods of responses to these two types of stimulation showed that impulses from area AI to area AII are directed both to input neurons for impulses from the medial geniculate body and to neurons at subsequent stages of the intracortical neuronal change. In response to stimulation of cortical area AI, disynaptic IPSPs appeared in many neurons of area AII. Only one IPSP with a latent period of 1.0 msec, regardable as monosynaptic, was recorded.     

c-Fos expression in rat brain stem and spinal cord in response to activation of cardiac ischemia-sensitive afferent neurons and electrostimulatory modulation

The purpose of this study was to identify central neuronal sites activated by stimulation of cardiac ischemia-sensitive afferent neurons and determine whether electrical stimulation of left vagal afferent fibers modified the pattern of neuronal activation. Fos-like immunoreactivity (Fos-LI) was used as an index of neuronal activation in selected levels of cervical and thoracic spinal cord and brain stem. Adult Sprague-Dawley rats were anesthetized with urethane and underwent intrapericardial infusion of an "inflammatory exudate solution" (IES) containing algogenic substances that are released during ischemia (10 mM adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine) or occlusion of the left anterior descending coronary artery (CoAO) to activate cardiac ischemia-sensitive (nociceptive) afferent fibers. IES and CoAO increased Fos-LI above resting levels in dorsal horns in laminae I-V at C2 and T4 and in the caudal nucleus tractus solitarius. Dorsal rhizotomy virtually eliminated Fos-LI in the spinal cord as well as the brain stem. Neuromodulation of the ischemic signal by electrical stimulation of the central end of the left thoracic vagus excited neurons at the cervical and brain stem level but inhibited neurons at the thoracic spinal cord during IES or CoAO. These results suggest that stimulation of the left thoracic vagus excites descending inhibitory pathways. Inhibition at the thoracic spinal level that suppresses the ischemic (nociceptive) input signal may occur by a short-loop descending pathway via signals from cervical propriospinal circuits and/or a longer-loop descending pathway via signals from the nucleus tractus solitarius.     

Corticofugal modulation of initial neural processing of sound information from the ipsilateral ear in the mouse

Background

Cortical neurons implement a high frequency-specific modulation of subcortical nuclei that includes the cochlear nucleus. Anatomical studies show that corticofugal fibers terminating in the auditory thalamus and midbrain are mostly ipsilateral. Differently, corticofugal fibers terminating in the cochlear nucleus are bilateral, which fits to the needs of binaural hearing that improves hearing quality. This leads to our hypothesis that corticofugal modulation of initial neural processing of sound information from the contralateral and ipsilateral ears could be equivalent or coordinated at the first sound processing level.

Methodology/Principal Findings

With the focal electrical stimulation of the auditory cortex and single unit recording, this study examined corticofugal modulation of the ipsilateral cochlear nucleus. The same methods and procedures as described in our previous study of corticofugal modulation of contralateral cochlear nucleus were employed simply for comparison. We found that focal electrical stimulation of cortical neurons induced substantial changes in the response magnitude, response latency and receptive field of ipsilateral cochlear nucleus neurons. Cortical stimulation facilitated auditory response and shortened the response latency of physiologically matched neurons whereas it inhibited auditory response and lengthened the response latency of unmatched neurons. Finally, cortical stimulation shifted the best frequencies of cochlear neurons towards those of stimulated cortical neurons.

Conclusion

Our data suggest that cortical neurons enable a high frequency-specific remodelling of sound information processing in the ipsilateral cochlear nucleus in the same manner as that in the contralateral cochlear nucleus.     

Corticofugal influences on segmental responses of lumbar spinal ventral horn interneurons in cats

Experiments on cats using extra- and intracellular recording methods showed that stimulation of the motor cortex of both hemispheres leads to considerable modulation of responses to stimulation of cutaneous and muscular lower limb afferents in spinal ventral horn interneurons in segments L6, 7. Three types of conditioning corticofugal effect were observed: facilitation, inhibition, and facilitation followed by inhibition (biphasic effect), and inhibitory effects predominated. The duration of facilitation of responses did not exceed 30–40 msec. The characteristics of the time course of inhibition varied: in some cases it began with relatively short intervals (8–15 msec), in other cases with an interval of 30–40 msec; its duration was 125–500 msec, or sometimes more. The effect of cortical stimulation on responses to stimulation of various afferent inputs of the same interneuron was shown to differ. The character of the conditioning corticofugal effect correlated with the latent period of segmental responses: facilitation was observed only in responses with a relatively short latent period (under 5 msec); responses with a longer latent period were mainly inhibited. The type of cortical effect also depended on the function performed by the activated afferent input. It is suggested that differential descending control of segmental polysynaptic responses recorded in ventral horn interneurons with wide convergence of afferent influences takes place in the initial stages of the reflex are. The mechanism of this control is discussed.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neiorofizologiya, Vol. 14, No. 6, pp. 563–571, November–December, 1982.     

c-fos expression in trigeminal spinal nucleus after electrical stimulation of the hypoglossal nerve in the rat

The expression of the immediate early gene, c-fos, was used to determine the distribution of brainstem neurons activated by stimulation of the distal hypoglossal nerve (XIIn) trunk. The traditional view of the XIIn is one of purely motor function; however, stimulation of XIIn excites neurons in the trigeminal spinal nucleus. The rationale for this study was to use c-fos expression as a marker for postsynaptic activity to define the pattern of brainstem neurons excited by XIIn stimulation. It was further hypothesized that if the afferent fibers that course within XIIn supply deep lingual tissues, then c-fos expression after direct stimulation of XIIn should display a pattern similar to that seen after chemical irritant stimulation of the deep tongue muscle. In barbiturate-anesthetized male rats electrical stimulation of XIIn produced a significant increase in Fospositive neurons in the dorsal paratrigeminal nucleus (dPa5) and laminae I-II of caudal subnucleus caudalis (Vc) and upper cervical dorsal horn. Mustard oil injection into the deep tongue muscle also produced an increase in c-fos expression in dPa5; however, the highest density of expression occurred in laminae I-II at the dorsomedial aspect of rostral Vc. Both electrical stimulation of XIIn and mustard oil stimulation of the deep tongue increased c-fos expression in the caudal ventrolateral medulla, an autonomic relay nucleus. These results suggest that one site of innervation for afferent fibers that travel within the distal trunk of XIIn is to supply the deep tongue muscle and to terminate in the dPa5. A second group of postsynaptic neurons activated only by XIIn stimulation was located in lamina I-II in caudal portions of Vc and upper cervical dorsal horn, a laminar distribution consistent with a role for XIIn afferents in sensory or autonomic aspects of lingual function.     

c-fos expression in trigeminal spinal nucleus after electrical stimulation of the hypoglossal nerve in the rat

The expression of the immediate early gene, c-fos, was used to determine the distribution of brainstem neurons activated by stimulation of the distal hypoglossal nerve (XIIn) trunk. The traditional view of the XIIn is one of purely motor function; however, stimulation of XIIn excites neurons in the trigeminal spinal nucleus. The rationale for this study was to use c-fos expression as a marker for postsynaptic activity to define the pattern of brainstem neurons excited by XIIn stimulation. It was further hypothesized that if the afferent fibers that course within XIIn supply deep lingual tissues, then c-fos expression after direct stimulation of XIIn should display a pattern similar to that seen after chemical irritant stimulation of the deep tongue muscle. In barbiturate-anesthetized male rats electrical stimulation of XIIn produced a significant increase in Fos-positive neurons in the dorsal paratrigeminal nucleus (dPa5) and laminae I-II of caudal subnucleus caudalis (Vc) and upper cervical dorsal horn. Mustard oil injection into the deep tongue muscle also produced an increase in c-fos expression in dPa5; however, the highest density of expression occurred in laminae I-II at the dorsomedial aspect of rostral Vc. Both electrical stimulation of XIIn and mustard oil stimulation of the deep tongue increased c-fos expression in the caudal ventrolateral medulla, an autonomic relay nucleus. These results suggest that one site of innervation for afferent fibers that travel within the distal trunk of XIIn is to supply the deep tongue muscle and to terminate in the dPa5. A second group of postsynaptic neurons activated only by XIIn stimulation was located in lamina I-II in caudal portions of Vc and upper cervical dorsal horn, a laminar distribution consistent with a role for XIIn afferents in sensory or autonomic aspects of lingual function.     

Physiological properties of afferents and synaptic reorganization in the rat cerebellum degranulated by postnatal X-irradiation.

Elimination of most granule, basket, and stellate interneurons in the rat cerebellum was achieved by repeated doses of low level x-irradiation applied during the first two weeks of postnatal life. Electrical stimulation of the brain stem and peripheral limbs was employed to investigate the properties of afferent cerebellar pathways and the nature of the reorganized neuronal synaptic circuitry in the degranulated cerebellum of the adult. Direct contacts of mossy fibers on Purkinje cells were indicated by short latency, single spike responses: 1.9 msec from the lateral reticular nucleus of brain stem and 5.4 msec from ipsilpateral forelimb. These were shorter than in normal rats by 0.9 and 2.1 msec, respectively. The topography of projections from peripheral stimulation was approximately normal. Mossy fiber responses followed stimulation at up to 20/sec, whereas climbing fiber pathways fatigued at 10/sec. The latency of climbing fiber input to peripheral limb stimulation in x-irradiated cerebellum was 23 +/- 8 (SD) msec. In x-irradiated rats, the climbing fiber pathways evoked highly variable extracellular burst responses and intracellular EPSPs of different, discrete sizes. These variable responses suggest that multiple climbing fibers contact single Purkinje cells. We conclude that each type of afferent retains identifying characteristics of transmission. However, rules for synaptic specification appear to break down so that: (1) abnormal classes of neurons develop synaptic connections, i.e., mossy fibers to Purkinje cells; (2) incorrect numbers of neurons share postsynaptic targets, i.e., more than one climbing fiber to a Purkinje cell; and (3) inhibitory synaptic actions may be carried out in the absence of the major inhibitory interneurons, i.e., Purkinje cell collaterals may be effective in lieu of basket and stellate cells.     

Physiological properties of afferents and synaptic reorganization in the rat cerebellum degranulated by postnatal x-irradiation

Elimination of most granule, basket, and stellate interneurons in the rat cerebellum was achieved by repeated doses of low level x-irradiation applied during the first two weeks of postnatal life. Electrical stimulation of the brain stem and peripheral limbs was employed to investigate the properties of afferent cerebellar pathways and the nature of the reorganized neuronal synaptic circuitry in the degranulated cerebellum of the adult. Direct contacts of mossy fibers on Purkinje cells were indicated by short latency, single spike responses: 1.9 msec from the lateral reticular nucleus of brain stem and 5.4 msec from ipsilateral forlimb. These were shorter than in normal rats by 0.9 and 2.1 msec, respectively. The topography of projections from peripheral stimulation was approximately normal. Mossy fiber responses followed stimulation at up to 20/sec, whereas climbing fiber pathways fatigued at 10/sec. The latency of climbing fiber input to peripheral limb stimulation in x-irradiated cerebellum was 23 ± 8 (SD) msec. In x-irradiated rats, the climbing fiber pathways evoked highly variable extracellular burst responses and intracellular EPSPs of different, discrete sizes. These variable responses suggest that multiple climbing fibers contact single Purkinje cells. We conclude that each type of afferent retains identifying characteristics of transmission. However, rules for synaptic specification appear to break down so that: (1) abnormal classes of neurons develop synaptic connections, i.e., mossy fibers to Purkinje cells; (2) incorrect numbers of neurons share postsynaptic targets, i.e., more than one climbing fiber to a Purkinje cell; and (3) inhibitory synaptic actions may be carried out in the absence of the major inhibitory interneurons, i.e., Purkinje cell collaterals may be effective in lieu of basket and stellate cells.