The origin of adaptation in the auditory pathway of locusts is specific to cell type and function.

We investigated the origin of spike frequency adaptation within a layered sensory network: the auditory pathway of locusts. Spike frequency adaptation as observed in an individual neuron may arise because of intrinsic or presynaptic adaptation mechanisms. To separate the contribution of different mechanisms, we recorded from the same cell during acoustic and intracellular current stimulation. We studied three identified neuron types that are representative for each network layer and participate in processing auditory patterns and localizing sound sources. By comparing current and acoustic stimulation, three distinct patterns of the distribution of adaptation mechanisms within the sensory network emerged: (1) balanced influence of both intrinsic and presynaptic adaptation mechanisms in an interneuron that summates over several receptor afferents (TN1), (2) predominantly inhibiting input as the source for spike frequency adaptation in a cell that transmits both pattern representation and directional information (BSN1), (3) primarily intrinsic, spike-triggered adaptation currents within an interneuron coding exclusively for direction (AN2). The time courses of spike frequency adaptation differed significantly between the cells types. Using the adaptation time constants, we were able to predict signal transmission properties for the different cells. We conclude that the adaptation mechanisms differ greatly among interneurons within this sensory pathway and are a function of their role in information processing.

Intracellular recordings from combination-sensitive neurons in the inferior colliculus.

In vertebrate auditory systems, specialized combination-sensitive neurons analyze complex vocal signals by integrating information across multiple frequency bands. We studied combination-sensitive interactions in neurons of the inferior colliculus (IC) of awake mustached bats, using intracellular somatic recording with sharp electrodes. Facilitated combinatorial neurons are coincidence detectors, showing maximum facilitation when excitation from low- and high-frequency stimuli coincide. Previous work showed that facilitatory interactions originate in the IC, require both low and high frequency-tuned glycinergic inputs, and are independent of glutamatergic inputs. These results suggest that glycinergic inputs evoke facilitation through either postinhibitory rebound or direct depolarizing mechanisms. However, in 35 of 36 facilitated neurons, we observed no evidence of low frequency-evoked transient hyperpolarization or depolarization that was closely related to response facilitation. Furthermore, we observed no evidence of shunting inhibition that might conceal inhibitory inputs. Since these facilitatory interactions originate in IC neurons, the results suggest that inputs underlying facilitation are electrically segregated from the soma. We also recorded inhibitory combinatorial interactions, in which low frequency sounds suppress responses to higher frequency signals. In 43% of 118 neurons, we observed low frequency-evoked hyperpolarizations associated with combinatorial inhibition. For these neurons, we conclude that low frequency-tuned inhibitory inputs terminate on neurons primarily excited by high-frequency signals; these inhibitory inputs may create or enhance inhibitory combinatorial interactions. In the remainder of inhibited combinatorial neurons (57%), we observed no evidence of low frequency-evoked hyperpolarizations, consistent with observations that inhibitory combinatorial responses may originate in lateral lemniscal nuclei.

Diversity of intersegmental auditory neurons in a bush cricket.

Various auditory interneurons of the duetting bush cricket Ancistrura nigrovittata with axons ascending to the brain are presented. In this species, more intersegmental sound-activated neurons have been identified than in any other bush cricket so far, among them a new type of ascending neuron with posterior soma in the prothoracic ganglion (AN4). These interneurons show not only morphological differences in the prothoracic ganglion and the brain, but also respond differently to carrier frequencies, intensity and direction. As a set of neurons, they show graded differences for all of these parameters. A response type not described among intersegmental neurons of crickets and other bush crickets so far is found in the AN3 neuron with a tonic response, broad frequency tuning and little directional dependence. All neurons, with the exception of AN3, respond in a relatively similar manner to the temporal patterns of the male song: phasically to high syllable repetitions and rhythmically to low syllable repetitions. The strongest coupling to the temporal pattern is found in TN1. In contrast to behavior the neuronal responses depend little on syllable duration. AN4, AN5 and TN1 respond well to the female song. AN4 (at higher intensities) and TN1 respond well to a complete duet.

Characterization of three different sensory fibers by use of neonatal capsaicin treatment, spinal antagonism and a novel electrical stimulation-induced paw flexion test.

In the present study, we first report an in vivo characterization of flexor responses induced by three distinct sine-wave stimuli in the electrical stimulation-induced paw flexion (EPF) test in mice. The fixed sine-wave electric stimulations of 5 Hz (C-fiber), 250 Hz (Adelta-fiber) and 2000 Hz (Abeta-fiber) to the hind paw of mice induced a paw-flexion response and vocalization. The average threshold for paw flexor responses by sine-wave stimulations was much lower than that for vocalization. Neonatally (P3) pretreatment with capsaicin to degenerate polymodal substance P-ergic C-fiber neurons increased the threshold to 5 Hz (C-fiber) stimuli, but not to 250 Hz (Adelta-fiber) and 2000 Hz (Abeta-fiber). The flexor responses to 5 Hz stimuli were significantly blocked by intrathecal (i.t.) pretreatment with both CP-99994 and MK-801, an NK1 and NMDA receptor antagonist, respectively, but not by CNQX, an AMPA/kainate receptor antagonist. On the other hand, the flexor responses induced by 250 Hz stimuli were blocked by MK-801 (i.t.) but not by CP-99994 or CNQX. In contrast, flexor responses induced by 2000 Hz stimuli were only blocked by CNQX treatment. These data suggest that we have identified three pharmacologically different categories of responses mediated through different primary afferent fibers. Furthermore, we also carried out characterization of the in vivo functional sensitivity of each of the sensory fiber types in nerve-injured mice using the EPF test, and found that the threshold to both 250 Hz and 2000 Hz stimulations were markedly decreased, whereas the threshold to 5 Hz stimulations was significantly increased. Thus we found opposing effects on specific sensory fiber-mediated responses as a result of nerve injury in mice. These results also suggest that the EPF analysis is useful for the evaluation of plasticity in sensory functions in animal disease models.

Synapse formation and mRNA localization in cultured Aplysia neurons.

mRNA localization and regulated translation provide a means of spatially restricting gene expression within neurons during axon guidance and long-term synaptic plasticity. Here we show that synapse formation specifically alters the localization of the mRNA encoding sensorin, a peptide neurotransmitter with neurotrophin-like properties. In isolated Aplysia sensory neurons, which do not form chemical synapses, sensorin mRNA is diffusely distributed throughout distal neurites. Upon contact with a target motor neuron, sensorin mRNA rapidly concentrates at synapses. This redistribution only occurs in the presence of a target motor neuron and parallels the distribution of sensorin protein. Reduction of sensorin mRNA, but not protein, with dsRNA inhibits synapse formation. Our results indicate that synapse formation can alter mRNA localization within individual neurons. They further suggest that translation of a specific localized mRNA, encoding the neuropeptide sensorin, is required for synapse formation between sensory and motor neurons.

Manual acupuncture needle stimulation of the rat hindlimb activates groups I, II, III and IV single afferent nerve fibers in the dorsal spinal roots.

Using single unit nerve recording techniques in rats, the present experiment aimed to determine which specific population of afferent nerve fibers (groups I, II, III and IV) in the dorsal roots at the 4th or 5th lumbar segments (L4 or L5) are activated during manual acupuncture needle stimulation. An acupuncture needle 300-340 microm in diameter was inserted into the skin and underlying muscles around the Zusanli acupoint (ST36) area in the hindlimbs, and was manually rotated right and left at a frequency of about 1 Hz for 1 min. The dorsal root of the L4 and L5 spinal nerve was cut close to the entrance into the spinal cord after laminectomy and dissected free to record unitary afferent nerve activity. A single afferent fiber activated by acupuncture stimulation was identified by the identical shape of the discharge spikes during stimulation and during electrically evoked action potentials induced by single pulse electrical stimulation of the sciatic nerve. The conduction velocity of the afferent fiber was calculated by the latency of the electrically evoked action potential. A total of 35 units were intentionally recorded from all animals in order to include all 4 afferent fiber groups. Units were spontaneously silent in the absence of stimulation, while all units responded to ipsilateral manual rotation of the acupuncture needle. The conduction velocity of all 35 units ranged between 0.8 and 86.0 m/s, thus belonging to groups I-V fibers. Mean conduction velocity of groups I, II, III and IV were 57.9 m/s (n = 13), 42.9 m/s (n = 11), 10.3 m/s (n = 6) and 1.2 m/s (n = 5), respectively. Mean discharge rates during acupuncture stimulation of groups I, II, III and IV afferents were 7.4 Hz, 6.2 Hz, 4.7 Hz and 0.4 Hz, respectively. Discharge rates of group IV afferent fibers were significantly lower than those of groups I, II and III afferents. It was concluded that manual acupuncture needle stimulation to the hindlimbs activated afferent nerve fibers belonging to all four groups of afferents in rats. It is suggested that all four groups of somatic afferents activated by manual acupuncture stimulation will elicit various effects when action potentials are delivered to the central nervous system.

Two populations of cold-sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor.

Cold sensing in mammals is not completely understood, although significant progress has been made recently with the cloning of two cold-activated ion channels, TRPM8 and TRPA1. We have used rat DRG neurons in primary culture and calcium fluorimetry to identify distinct populations of cold-sensitive neurons, which may underlie different functions. Menthol sensitivity clearly separated two classes of cold-responding neurons. One group was menthol-sensitive (MS), was activated at warmer temperatures and responded faster and with a larger increase in intracellular calcium concentration during cooling; the fraction of MS neurons in culture and their cold sensitivity were both increased in the presence of nerve growth factor. Neurons in the menthol-insensitive (MI) group required stronger cooling for activation than MS cells and neither their proportion nor their cold sensitivity were significantly altered by nerve growth factor. The two groups of cold-sensitive neurons also had different pharmacology. A larger fraction of MS cells were capsaicin-sensitive and coexpression of menthol and capsaicin sensitivity was observed in the absence of NGF. MI neurons were not stimulated by the super-cooling agent icilin or by the irritant mustard oil. Taken together these findings support a picture in which TRPM8 is the major player in detecting gentle cooling, while TRPA1 does not seem to be involved in cold sensing by MI neurons, at least in the temperature range between 32 and 12 degrees C.

BTB/POZ-zinc finger protein abrupt suppresses dendritic branching in a neuronal subtype-specific and dosage-dependent manner.

How dendrites of different neuronal subtypes exhibit distinct branching patterns during development remains largely unknown. Here we report the mapping and identification of loss-of-function mutations in the abrupt (ab) gene that increased the number of dendritic branches of multiple dendritic (MD) sensory neurons in Drosophila embryos. Ab encodes an evolutionarily conserved transcription factor that contains a BTB/POZ domain and C2H2 zinc finger motifs. We show that ab has a cell-autonomous function in postmitotic neurons to limit dendritic branching. Ab and the homeodomain protein Cut are expressed in distinct but complementary subsets of MD neurons, and Ab functions in a transcriptional program that does not require Cut. Deleting one copy of ab or overexpressing ab had opposite effects on the formation of higher-order dendritic branches, suggesting that the Ab level in a specific neuron directly regulates dendritic complexity. These results demonstrate that dendritic branching can be suppressed by neuronal subtype-specific transcription factors in a cell-autonomous and dosage-dependent manner.

Neurophysiological identification and characterization of thalamic neurons with single unit recording in essential tremor patients.

This study investigated the characteristics of the neuronal activities of the motor thalamus (Vim and Vop) in essential tremor (ET) patients, and compared the results with those of Parkinson's disease (PD) patients. The kinetic (Ki) neurons were found mainly in the Vim, whereas the voluntary (Vo) neurons were found principally in the Vop of ET patients. The mean firing rates of the ET patients were higher than those of the PD patients. In addition, the mean firing rates of the Ki neurons of the ET patients were higher than those of the PD patients in the Vim nuclei. However, the mean firing rates of the ventralis caudalis (Vc) neurons, which respond to sensory stimulation, were similar in each group. An analysis of the incidence of bursting neurons revealed that the Vop nucleus of the ET patients had less bursting neurons than the PD patients. However, in the Vim nucleus, both groups possessed bursting neurons even though the incidence was slightly different. Tremor cells were observed less frequently in the Vim nucleus of ET patients than in the PD patients. This study demonstrated the characteristic features of the neuronal activities of ET patients compared to those of PD patients.

Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch.

We found a class of lamina I spinothalamic tract (STT) neurons selectively excited by iontophoretic histamine. The responses of this class of neurons parallel the pure itching sensation this stimulus elicits in humans, and match the responses of peripheral C-fibers that have similar selectivity. These neurons have distinct central conduction velocities and thalamic projections, indicating that they constitute a unique subset of STT neurons. These findings can explain why a lesion of the lateral STT disrupts itch along with pain and temperature sensations. Our findings provide strong evidence that itch is subserved by specific neural elements both peripherally and centrally.

The distribution fields of sensory neurons in the human thalamus.

Thalamic neurons were identified by activity related to passive joint movement, active joint movement, tapping stimulation, and light touch stimulation during surgery to treat movement disorders. The neurons were classified into three types: movement-related neurons, tapping-related neurons, or superficial sensory neurons. Tapping-related neurons had characteristics of lemniscal sensory neurons and occupied the border area of movement-related neurons and superficial sensory neurons. Tapping-related neurons showed a laminar distribution 1.0-1.5 mm in width in the anterodorsal region of the nucleus ventrocaudalis. Results suggest that the distribution pattern of tapping-related neurons in the human thalamus is consistent with the functional distribution pattern found in the monkey thalamus.

Corticotropin releasing factor-containing afferents to the lateral septum of the rat brain.

Corticotropin releasing factor (CRF)-containing afferents to the rat lateral septum (LS) have been determined by means of cobalt-enhanced immunohistochemistry, tracing of retrograde transport of horseradish peroxidase (HRP), and by lesioning experiments. When unilateral lesions included the rostral part of the hypothalamus, CRF-like immunoreactive (CRFI) ipsilateral fibers in the LS decreased in number. Lesions in other brain regions did not cause alterations in the septal CRFI fibers. These findings suggest that the septal CRFI fibers originate in the rostral part of the hypothalamus. Furthermore, combined HRP and immunohistochemical staining on the same sections demonstrated double-labeled cells in two discrete areas within the rostral hypothalamus: one was the perifornical hypothalamic area (PeF) at the level of the paraventricular hypothalamic nucleus, and the other was the most caudal part of the anterior hypothalamic nucleus (AHc). These findings show that a large proportion of the CRFI projections to the LS have their origins in the PeF and AHc.

The primate spinocervicothalamic pathway: responses of cells of the lateral cervical nucleus and spinocervical tract to innocuous and noxious stimuli.

1. The response properties of neurons of the spinocervicothalamic pathway were studied in anesthetized macaque monkeys. Graded innocuous and noxious mechanical stimuli, including sinusoidal vibration and thermal pulses, were applied to the cutaneous receptive fields. 2. Forty-nine cells in the lateral cervical nucleus (LCN) were identified by antidromic activation from the ventral posterior lateral (VPL) nucleus of the contralateral thalamus. Twelve spinocervical tract (SCT) cells in the lumbosacral enlargement of the spinal cord were identified by antidromic activation from stimulation of the ipsilateral dorsolateral funiculus below C3 but not above C1. 3. Latencies for antidromic activation of LCN neurons averaged 2.3 ms, corresponding to a mean conduction velocity of approximately 17 m/s. Mean latency for orthodromic activation of LCN neurons following electrical stimulation of peripheral nerves was 12.6 ms. Overall mean conduction velocity for the monkey spinocervicothalamic pathway was estimated to be 29 m/s. 4. Most LCN cells had receptive fields on hairy skin, but some had input from glabrous skin and a few had subcutaneous fields. The receptive fields of most SCT cells had a glabrous skin component. Receptive fields tended to be smaller for SCT than LCN cells even for fields on a comparable part of the distal hindlimb. 5. Based on their responses to a series of mechanical stimuli (brushing, pressure, pinch, and squeeze), LCN and SCT cells were classified as low-threshold (LT), wide dynamic range (WDR), or high-threshold (HT) neurons. Most of the cells were in the LT or WDR classes. Thus the spinocervicothalamic pathway in the monkey differs from the spinothalamic tract (STT), in that STT cells are generally of the WDR or HT classes. 6. With the use of discriminant analysis, LCN and SCT neurons were allocated to categories determined from a k-means cluster analysis of the responses of 318 STT cells. The LCN and SCT neurons were in different proportions in the various categories than were STT cells, suggesting differences in the signaling properties of the spinocervicothalamic and spinothalamic paths. 7. Innocuous steady indentation of the skin failed to excite any of the neurons tested. Thus no positive evidence was obtained for an input to LCN neurons from slowly adapting mechanoreceptors. 8. Sinusoidal vibratory stimuli were used to test the ability of LCN and SCT neurons to follow repeated innocuous mechanical stimuli. Vibration at 10 Hz and an amplitude of 100 micron resulted in repetitive discharges in most LCN neurons and half the SCT neurons tested; many LCN neurons had thresholds below 25 micron.(ABSTRACT TRUNCATED AT 400 WORDS)

Topography of binaural organization in primary auditory cortex of the cat: effects of changing interaural intensity.

Responses from neuron clusters were used to derive binaural and aural dominance maps within the 5- to 30-kHz frequency representation of the primary auditory cortical (AI) field in the barbiturate-anesthetized cat. Tone burst stimuli were presented dichotically using a calibrated and sealed acoustic delivery system to parametrically vary interaural intensity difference (IID). Neuron cluster responses were divided into three binaural interaction classes using audiovisual criteria: summation (56%), suppression (25%), and mixed (17%). Neurons in the summation and suppression classes demonstrated a single type of binaural interaction, regardless of intensity manipulations. Neurons in the mixed binaural class demonstrated summation responses when dichotic tonal intensities were near their threshold levels and the IID was small, but suppression responses when the IID was increased. The relative proportions of the three binaural interaction classes changed with distance along the dorsal-to-ventral isofrequency dimension. Nearly equal proportions of each class were observed at the ventral end of field AI, whereas quite different proportions of each class were seen at the dorsal extreme of the field. The average frequency of occurrence of the mixed binaural class increased nearly monotonically with increasing distance from the dorsal end of field AI. The majority of mapped AI loci exhibited a contralateral aural dominance (65%) with equidominance (25%), ipsilateral aural dominance (6%), and predominantly binaural (4%) classes accounting for the remainder. Average topographic distributions of aural dominance suggested that the ventral end of field AI consisted almost exclusively of the contralateral dominance class, whereas more equal proportions of the four classes were observed near the dorsal extreme of the field. The highest average proportions of ipsilateral aural dominance and predominantly binaural classes were found in the dorsal half of field AI. Single neurons, isolated at cortical loci assigned to the mixed binaural class during the mapping of neuron clusters, were shown to demonstrate both summation and suppression responses. Quantitative measurements relating either discharge rate or response latency to changes in the IID appeared to distinguish these cells from other single neurons studied. Typically, the probability of discharge was initially increased and subsequently decreased by progressive changes in IID that increased the intensity of the ipsilateral tone relative to the contralateral tone. The initial changes in IID characteristically shortened the latent period to the binaural response while subsequent increments in IID produced a more comp

Classification of primate spinothalamic and somatosensory thalamic neurons based on cluster analysis.

Data analyzed in this study were derived from the responses of 128 spinothalamic tract (STT) cells and 110 thalamic neurons recorded in 75 anesthetized monkeys. A k-means cluster analysis, a nonhierarchical clustering technique, was performed using the relative magnitudes of responses to a graded series of innocuous and noxious mechanical stimuli applied to the receptive field. For comparison, a parallel analysis was performed based on definitions of low-threshold (LT), wide dynamic range (WDR), and high-threshold (HT) cells used by our laboratory. For 128 STT cells, a classification scheme with three clusters was found statistically to be the best. This yielded groups of 22, 57, and 49 cells in clusters 1, 2, and 3, respectively. Cluster 1 cells were activated best by low-intensity mechanical stimuli, whereas cluster 3 cells were activated primarily by nociceptive stimuli. Cluster 2 cells had intermediate characteristics. When the classification scheme based on the cluster analysis was compared with the classification of the same neurons as LT, WDR, and HT cells, cluster 1 cells were divided into LT and WDR cells, whereas cluster 2 and 3 cells included WDR and HT cells. For 110 thalamic neurons, a classification scheme with five clusters was found statistically to be the best. Clusters 1-5 contained 25, 34, 17, 10, and 24 cells, respectively. Response characteristics of cells in each group indicated a gradual change in sensitivity to higher intensities of peripheral input from cluster 1 to 5. When this classification scheme was compared with the classification scheme previously used by our laboratory, cluster 1 cells belonged to the LT group, clusters 2 and 3 split into LT and WDR cells, and clusters 4 and 5 included WDR and HT cells. It is concluded that a classification scheme based on a cluster analysis of the responses of neurons to standardized stimuli may provide an objective and functionally meaningful way to categorize somatosensory neurons.

Responses of primate spinothalamic neurons to noxious thermal stimulation of glabrous and hairy skin.

Extracellular recordings were made from 81 primate spinothalamic (STT) neurons in the L7-S1 segments of the spinal cord. The majority of the sample was recorded from within laminae IV-V. The responses of STT neurons to noxious thermal stimulation of glabrous and hairy skin were studied in an attempt to identify a neural substrate for the differences in thermal sensation evoked by noxious stimulation of these two types of skin. In addition, the responses to graded mechanical stimuli were examined for evidence of differential sensitivity. Thermal intensity-response functions were constructed from the alteration in the mean discharge rate produced by a 30-s thermal pulse of 43-55 degrees C. Generally, the functions derived from stimulation of both hairy and glabrous skin were either linear or positively accelerating. Deceleration in the response functions was occasionally observed above 53 degrees C. The population mean discharge rate derived from glabrous skin stimulation was significantly greater than that derived from hairy skin stimulation above 49 degrees C. Cluster analysis was used to assess whether the STT population could be partitioned into functionally relevant subgroups. No clustering was evident on the basis of the alteration in discharge rate during stimulation alone. Analysis of the alteration in mean discharge rate during and following thermal stimulation identified four groups; these were referred to as the Amnr, Bmnr, Cmnr, and Dmnr classes. The clustering was not dependent on differences in the responses evoked from hairy and glabrous skin. The mechanical and thermal sensitivities of each thermal class covaried. The capacity of the STT population to code the quality of noxious thermal stimuli, as judged by changes in the across-neuron discharge pattern, was assessed with a multidimensional scaling technique (MDS). The results suggest that the population discharge could be used to order stimuli correctly from 45 to 55 degrees C. Also, it was found that a substantial change in the population's discharge pattern occurred to stimuli between 47 and 49 degrees C when delivered to hairy skin. A similar alteration in the population's discharge pattern occurred to glabrous skin stimuli near 51 degrees C. These alterations in population behavior may underly the alterations in sensory quality in humans that occur in these temperature ranges when stimulating hairy and glabrous skin. The possible roles of the thermally and mechanically based classes in thermal intensity and quality coding were examined. Within the lower intensity ranges (less than 49-51 degrees C), the Cmnr and Dmnr classes appeared to be best suited to intensity coding.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuronal activities in ventrobasal complex of thalamus and in trigeminal main sensory nucleus during EEG desynchronization in anesthetized rats.

Activities of somatosensory relay neurons responding to orofacial mechanical stimulation were examined in the ventrobasal complex of the thalamus (VB) and in the trigeminal main sensory nucleus (MSN) during EEG desynchronization in urethane-anesthetized rats. EEG desynchronization was induced by scrotal warming in a temperature range of 35-40 degrees C. Responses of most VB neurons to receptive-field stimulation were augmented during EEG desynchronization, when compared to responses during synchronization. Spontaneous activity of VB neurons also increased with EEG desynchronization. Responses of MSN neurons to receptive-field stimulation did not change appreciably when the EEG pattern was altered. If a VB neuron was induced by iontophoretic application of glutamate to fire at the same rate as seen during EEG desynchronization, a similar increased response to receptive-field stimuli was also observed. The augmented response of the VB neuron during desynchronization may thus have resulted from increased excitability of the neuron itself.

Periventricular gray inhibition of thoracic spinothalamic cells projecting to medial and lateral thalamus.

Effects of electrical stimulation of the periventricular gray (PVG) on spinothalamic tract (STT) cell activity were determined in 19 anesthetized monkeys (Macaca fascicularis). Twenty-two STT cells projected to the ventral posterior lateral nucleus (L-STT cells), 11 to the medial thalamus (M-STT cells), and 9 to both thalamic regions (LM-STT cells). All cells had somatic receptive fields and responded to electrical stimulation of cardiopulmonary sympathetic afferent fibers. PVG stimulation inhibited activity of 41 of 42 STT cells. Degree of inhibition of background activity was related to intensity and frequency. Stimulus currents of 300 microA or less completely silenced background activity of most cells. Thresholds for stimulus current averaged 100 +/- 20 microA and were unrelated to cell projection site, laminar location, or type of somatic or visceral input. However, lowest thresholds were found when the PVG electrodes were located within 0.5 mm of the third ventricle in the dorsomedial hypothalamus or nucleus reuniens of the thalamus. PVG stimulation inhibited responses of 22 of 22 cells to intracardiac injections of bradykinin. Bradykinin (2 micrograms/kg) increased cell activity from 15 +/- 3 to 31 +/- 5 spikes/s (P less than 0.01), and PVG stimulation (380 +/- 40 microA) reduced activity to 9 +/- 3 spikes/s (P less than 0.001). PVG stimulation inhibited responses of 33 of 33 STT cells to noxious pinch of skin or skin and muscle and responses of 8 of 8 cells to hair movement. Degree of inhibition of cell responses to noxious pinch was not significantly different from inhibition of responses to bradykinin. Effects of PVG stimulation on activity of six STT cells were studied before and after bilateral lesions were made in the dorsolateral funiculus (DLF). In no case did the lesions abolish or attenuate inhibitory effects of PVG stimulation. These results suggest that PVG may participate in descending inhibition of STT cells including cells mediating cardiac pain. The descending pathways are not located in the DLF. Further, descending inhibitory systems modulate STT cells projecting to both medial and lateral thalamus.

The spinothalamic system of the rat. I. Locations of cells of origin.

Horseradish peroxidase retrograde transport has been used to locate neurons of the rat spinal cord and lower medulla that project to the thalamus. Eight groups of spinothalamic cells are identified, some of which are anatomically continuous with thalamically projecting groups in the lower medulla. Most of the groups are seen only at the highest cervical levels, and several of them have not been previously recognised as spinothalamic relays. They are marginal layer (M), ventral border of the substantia gelatinosa (SGv), neck of the dorsal horn (N), lateral cervical nucleus (LCN), ventromedial portion of the dorsal horn (DHvm), intermediate gray zone (IGZ), dorsal portion of the ventral horn (VHd), and ventral portion of the ventral horn (VHv). Most of the cell bodies are contralateral to their thalamic terminations; only the VHd group is ipsilateral. The major finding conflicts with traditional concepts of the spinothalamic system, and concerns the rostrocaudal distribution of the cells of origin. With the sole exception of the DHvm group, the great majority of the thalamically projecting neurons of the rat are confined to the most rostral spinal levels (medulla/cord junction through C4). Below C4, most of the spinothalamic cells are concentrated in a single DHvm group between levels T9 and L4, probably concerned with hindlimb proprioception. The spinothalamic groups at high cervical levels may be relays for information ascending from lower regions. This might help to explain why, in man, surgical destruction of fibres crossing the midline in a single high cervical segment can cause a loss of pain sensation over most of the body.

The organization of neural inputs to the medial preoptic nucleus of the rat.

There is general agreement that the medial preoptic nucleus (MPN) receives projections from widespread regions of the brain, although there are significant discrepancies in the literature with regard to certain specific inputs. Therefore, we have reexamined the inputs to this nucleus with both retrograde and anterograde axonal transport techniques. First, injections of the retrograde tracers true blue, SITS, or wheat germ agglutinin were made into the region of the MPN and the distribution of retrogradely labeled cells was charted. Then, autoradiographic material was used to confirm the results of the retrograde studies, to identify the route taken by fibers projecting to the MPN, and to describe the distribution of projections with respect to the three cytoarchitectonic subdivisions of the nucleus. The results indicate that the MPN receives inputs from widely distributed areas in both the forebrain and brainstem, and that these inputs appear to be distributed topographically within the three cytoarchitectonic subdivisions of the nucleus. Direct inputs to the MPN arise from all major areas of the hypothalamus (except for the median and magnocellular preoptic nuclei, the supraoptic and suprachiasmatic nuclei, and the medial and lateral mammillary nuclei). Projections from nuclei within the periventricular zone of the hypothalamus end primarily in the medial part of the MPN, while inputs from the lateral zone are mainly confined to the lateral part of the nucleus, as are projections from the nuclei within the medial zone, except for those from the anterior and ventromedial nuclei, which appear to be more widespread. The MPN receives major inputs from limbic regions including the amygdala, ventral subiculum, and ventral lateral septal nucleus, all of which end preferentially in the lateral part of the MPN. In contrast, the projection from the encapsulated part of the bed nucleus of the stria terminalis appears to end preferentially in the central part of the MPN and in immediately adjacent regions of the medial subdivision. In addition, the MPN may receive relatively sparse inputs from infralimbic and insular cortical areas, the nucleus accumbens, and the substantia innominata. Finally, ascending serotoninergic projections from the raphe nuclei appear to terminate principally in the lateral part of the MPN, whereas inputs from regions containing noradrenergic cell groups are chiefly distributed to the central and medial parts of the nucleus. Other brainstem regions that appear to provide modest inputs include the ventral tegmental area, central tegmental field, periaqueductal gray, pedunculopontine nucleus, and the peripeduncular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)