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Neurochemical investigation of the afferent pathway from the vagus nerve to the nucleus tractus solitarius in mediating the "satiety syndrome" induced by systemic cholecystokinin.

The satiety syndrome induced by intraperitoneally administered cholecystokinin (CCK) requires an intact visceral sensory feedback system involving the afferent vagus nerve and the nucleus tractus solitarius (NTS). Since both the vagus and the NTS contain CCK, the vagal-NTS synapse could conceivably employ CCK as a transmitter. To test this hypothesis, CCK was injected directly into the NTS region in awake rats. CCK at doses of 1 ng, 10 ng, and 100 ng had no effect on food consumption or exploratory behaviors associated with the satiety syndrome. The acetylcholine agonist carbachol, injected directly into the NTS region, effectively mimicked the actions of intraperitoneally administered CCK on feeding and exploration. These data suggest that CCK is not the transmitter at the vagal-NTS site in the visceral sensory pathway projecting to brain regions mediating the reduced feeding and exploration actions of systemic CCK.

Afferent Pathways↗

Somatosensory responses in the cat motor cortex. I. Identification and course of an afferent pathway.

1. The main aim of the present series of experiments was to demonstrate with electrophysiological methods that the spinothalamocortical system may send somesthetic information to the pyramidal and corticospinal tract cells in the motor cortex of the cat. 2. Experiments were carried out on acutely prepared cats anesthetized with alpha-chloralose. Extra- and intracellular recordings were made from the cells located in the pericruciate motor cortex (the lateral portion of area 4 gamma). They were identified by their antidromic responses to pyramidal stimulation and/or stimulation of the dorsolateral funiculus of the spinal cord. The animals were subjected to a set of nervous tissue lesions to prevent any transit of extereoceptive information to the motor cortex via the cerebellum and the somatosensory cortex. A lesion of the dorsal part of the spinal cord was also made, leaving intact only the afferent inflow ascending in the spinal ventral half, i.e., the spinothalamic system. 3. In this cat preparation it was observed that both electrical and natural stimulation of the limbs still efficiently activated the motor cortical efferent cells. 4. The pathway was mapped by applying microstimulation along its whole course in the spinal cord and brain stem. Stimulation of the primary afferent fibers running in the dorsal columns caudally to the spinal cord lesion produced activation and/or inhibition of the cortical cells. The existence of these responses may be attributable to the existence of collaterals from primary afferent fibers located in the dorsal columns, which activate the spinothalamic tract cells either mono- or polysynaptically. In the brain stem the fibers join the medial lemniscus. 5. In view of the short latency of the responses (mean latency 10.5 ms from the spinal cord) it is suggested that this component of the spinothalamic system may play an important role in the sensory regulation of ongoing movements.

Afferent Pathways↗

The recovery of postural reflexes and locomotion following low thoracic hemisection in adult cats involves compensation by undamaged primary afferent pathways.

Spinal hemisection in the adult cat results in motor impairments followed by substantial recovery of function (16, 20, 39, 53). The present study was undertaken to assess the contribution of undamaged ipsilateral segmental and contralateral descending systems to recovery of motor function. Quantitative behavioral methods were used to examine monopedal reflex and bipedal locomotor functions after thoracic hemisection. Different facets of motor behavior recover at different times. The recovery of monopedal postural reflexes precedes the recovery of more complex motor behavior. Since the reflexes tested are initiated by segmental afferent input and show recovery and normal motor patterns during locomotion, as defined by kinematic analysis show recovery, it is likely that dorsal root input compensates for the loss of descending input to one side of the spinal cord. Quantitative immunocytochemical methods for visualizing the central projections of dorsal root fibers (monoclonal antibody RAT-102; 49) and the descending serotoninergic pathway were used to examine the response of these pathways to hemisection. Hemisection results in a permanent decrease in the density of serotoninergic projections and a permanent increase in dorsal root projections in the spinal cord. The increased density of RAT-102 may represent an increase in the projection of dorsal root fibers and provide the increased input necessary to mediate enhanced reflex control. A transient increase in GAP-43 in the dorsal horn ipsilateral to the hemisection suggests that the increased density of RAT-102 immunoreactivity is associated with growth. Taken together, our results suggest that sprouting of primary afferents within the spinal cord is one mechanism underlying the recovery of function after hemisection.

Adaptation, Physiological↗

Role of afferent pathways of heat and cold in body temperature regulation.

The detection of surface and internal temperatures is achieved by axons terminating at lamina I of the spinal dorsal horn, otherwise approached only by nociceptive afferents. Recent advances in thermal physiology research have disclosed that temperature-sensitive ion channels belonging to the "transient receptor potential" family exist in the peripheral sensory neurons and in the brain. Thermosensory, nociceptive and polymodal afferents project to different thalamic nuclei, and specific pathways to the insular cortex evoke the conscious experience of thermal sensation. The posterior insular region represents discriminative thermal sensation, while the largest correlation with subjective ratings of temperature is located in the orbitofrontal and anterior insular cortex. The insular cortex forms an integrative part of the limbic system and is closely tied with the hypothalamus, the amygdala, the anterior cingulate cortex and the orbitofrontal cortex and emerges as the main coordinator of behavioral, autonomic and endocrine responses to both non-noxious and noxious thermal stimuli. The firing rate of warm and cold receptors is not altered by pyrogens. A strong correlation between the onset of fever and production of superoxide by macrophages following the injection of pyrogens implicates reactive oxygen species as elicitors of fever, a hypothesis strengthened by the observation that oxygen radical scavengers or thiol reductants act as antipyretics. Oxidative stress appears to be sensed by the brain and a likely structure for its detection may be the redox-sensitive site of the N-methyl-D-aspartate (NMDA) receptor for glutamate, in that oxidation of this site causes fever while its reduction lowers body temperature, effects which are abrogated by specific NMDA receptor blockers.

Animals↗

Modulation of transmission in the corticospinal and group Ia afferent pathways to soleus motoneurons during bicycling.

Transmission in the corticospinal and Ia pathways to soleus motoneurons was investigated in healthy human subjects during bicycling. Soleus H reflexes and motor evoked potentials (MEPs) after transcranial magnetic stimulation (TMS) were modulated similarly during the crank cycle being large during downstroke [concomitant with soleus background electromyographic (EMG) activity] and small during upstroke. Tibialis anterior MEPs were in contrast large during upstroke and small during downstroke. The soleus H reflexes and MEPs were also recorded during tonic plantarflexion at a similar ankle joint position, corresponding ankle angle, and matched background EMG activity as during the different phases of bicycling. Relative to their size during tonic plantarflexion, the MEPs were found to be facilitated in the early part of downstroke during bicycling, whereas the H reflexes were depressed in the late part of downstroke. The intensity of TMS was decreased below MEP threshold and used to condition the soleus H reflex. At short intervals (conditioning-test intervals of -3 to -1 ms), TMS produced a facilitation of the H reflex that is in all likelihood caused by activation of the fast monosynaptic corticospinal pathway. This facilitation was significantly larger in the early part of downstroke during bicycling than during tonic plantarflexion. This suggests that the increased MEP during downstroke was caused by changes in transmission in the fast monosynaptic corticospinal pathway. To investigate whether the depression of H reflexes in the late part of downstroke was caused by increased presynaptic inhibition of Ia afferents, the soleus H reflex was conditioned by stimulation of the femoral nerve. At a short interval (conditioning-test interval: -7 to -5 ms), the femoral nerve stimulation produced a facilitation of the H reflex that is mediated by the heteronymous monosynaptic Ia pathway from the femoral nerve to soleus motoneurons. Within the initial 0.5 ms after its onset, the size of this facilitation depends on the level of presynaptic inhibition of the Ia afferents, which mediate the facilitation. The size of the facilitation was strongly depressed in the late part of downstroke, compared with the early part of downstroke, suggesting that increased presynaptic inhibition was indeed responsible for the depression of the H reflex. These findings suggest that there is a selectively increased transmission in the fast monosynaptic corticospinal pathway to soleus motoneurons in early downstroke during bicycling. It would seem likely that one cause of this is increased excitability of the involved cortical neurons. The increased presynaptic inhibition of Ia afferents in late downstroke may be of importance for depression of stretch reflex activity before and during upstroke.

Adult↗

Cervical afferent pathway to inferior oblique motoneuron in the cat.

The neuronal pathway implicated in the vertical cervico-ocular reflex (COR) was investigated electrophysiologically in chloralose anesthetized cats. The effect of bilateral C2 dorsal root afferent stimulation on inferior oblique motoneurons (IO-MN) was investigated by intracellular recording. Control disynaptic excitatory postsynaptic potentials elicited in IO-MNs following stimulation of the contralateral anterior semicircular canal nerve (ACN) were invariably facilitated by conditioning stimulation to both ipsilateral and contralateral C2 dorsal roots (DR) in all motoneurons tested. This result indicates that inputs from the C2 DR of both sides and the contralateral ACN converge onto secondary vestibular neurons ('common interneurons') which project directly to the IO-MN. Common interneurons mediating vestibular and cervical excitation to the IO-MNs were studied in the vestibular nuclei on the side opposite to the motoneurons by extracellular recording. Nineteen vestibular neurons were identified as common interneurons; they were distributed in the caudal half of the lateral nucleus and the rostral half of the descending nucleus. The present experiment provides electrophysiological evidence of the projection of upper cervical afferents to the ipsilateral vestibular nuclei. The difference in neuronal organization between the horizontal and vertical COR is also briefly discussed.

Action Potentials↗

[Ultrastrastructural and histochemical examinations of afferent pathways of the geniculate-cortical relay cells].

On the basis of ultrastructural and ultrahistochemical studies in the dorsal part of lateral geniculate nucleus (d LGN) of albino rat a topistical model of geniculo-cortical relay cell (GCR-cell) afferentiation is proposed. Retinal afferent terminals of type 2a and 2b and their synaptic properties are discussed in connection with slow and fast conducting retinofugal channels. Interneuronal contacts are represented by presynaptic dendritic specializations (P-bouton) and by axonal terminals (F-bouton) (LIEBERMAN and WEBSTER, 1974). These findings suggest that the function of interneurons may be dualistic. Cortical afferents are represented by small terminals with round agranular vesicles. Using the "false" transmitter 5-OH-DA we succeeded in demonstrating degenerating terminals with dense core vesicles. There is evidence that noradrenergic axons originating in the Locus coeruleus may contact with the distal dendritic parts of GCR-neurons.

Acetylcholinesterase↗