Responses of primate SI cortical neurons to noxious stimuli

Recordings were made from single SI cortical neurons in the anesthetized macaque monkey. Each isolated cortical neuron was tested for responses to a standard series of mechanical stimuli. The stimuli included brushing the skin, pressure, and pinch. The majority of cortical neurons responded with the greatest discharge frequency to brushing the receptive field, but neurons were found in areas 3b and 1 that responded maximally to pinching the receptive field. A total of 68 cortical nociceptive neurons were examined in 10 animals. Cortical neurons that responded maximally to pinching the skin were also tested for responses to graded noxious heat pulses (from 35 to 43, 45, 47, and 50 degrees C). If the neuron failed to respond or only responded to 50 degrees C, the receptive field was also heated to temperatures of 53 and 55 degrees C. Fifty-six of the total population of nociceptive neurons were tested for responses to the complete series of noxious heat pulses: 46 (80%) exhibited a progressive increase in the discharge frequency as a function of stimulus intensity, and the spontaneous activity of two (4%) was inhibited. One population of cortical nociceptive neurons possessed restricted, contralateral receptive fields. These cells encoded the intensity of noxious mechanical and thermal stimulation. Sensitization of primary afferent nociceptors was reflected in the responses of SI cortical nociceptive neurons when the ascending series of noxious thermal stimulation was repeated. The population of cortical nociceptive neurons with restricted receptive fields exhibited no adaptation in the response during noxious heat pulses of 47 and 50 degrees C. At higher temperatures the response often continued to increase during the stimulus. The other population of cortical nociceptive neurons was found to have restricted, low-threshold receptive fields on the contralateral hindlimb and, in addition, could be activated only by intense pinching or noxious thermal stimuli delivered on any portion of the body. The stimulus-response functions obtained from noxious thermal stimulation of the contralateral hindlimb were not different from cortical nociceptive neurons with small receptive fields. However, nociceptive neurons with large receptive fields exhibited a consistent adaptation during a noxious heat pulse of 47 and 50 degrees C. Based on the response characteristics of these two populations of cortical nociceptive neurons, we conclude that neurons with small receptive fields possess the ability to provide information about the localization, the intensity, and the temporal attributes of a noxious stimulus.4+.     

Responses to task-irrelevant visual features by primate prefrontal neurons

The primate brain is equipped with prefrontal circuits for interpreting visual information, but how these circuits deal with competing stimulus-response (S-R) associations remains unknown. Here we show different types of responses to task-irrelevant visual features in three functionally dissociated groups of primate prefrontal neurons. Two Japanese macaques participated in a go/no-go task in which they had to discriminate either the color or the motion direction of a visual target to make a correct manual response. Prior to the experiment, the monkeys had been trained extensively so that they acquired fixed associations between visual features and required responses (e.g., "green = go"; "downward motion = no-go"). In this design, the monkey was confronted with a visual target from which it had to extract relevant information (e.g., color in the color-discrimination condition) while ignoring irrelevant information (e.g., motion direction in the color-discrimination condition). We recorded from 436 task-related prefrontal neurons while the monkey performed the multidimensional go/no-go task: 139 (32%) neurons showed go/no-go discrimination based on color as well as motion direction ("integration cells"); 192 neurons (44%) showed go/no-go discrimination only based on color ("color-feature cells"); and 105 neurons (24%) showed go/no-go discrimination only based on motion direction ("motion-feature cells"). Overall, however, 162 neurons (37%) were influenced by irrelevant information: 53 neurons (38%) among integration cells, 71 neurons (37%) among color-feature cells, and 38 neurons (36%) among motion-feature cells. Across all types of neurons, the response to an irrelevant feature was positively correlated with the response to the same feature when it was relevant, indicating that the influence from irrelevant information is a residual from S-R associations that are relevant in a different context. Temporal and anatomical differences among integration, color-feature and motion-feature cells suggested a sequential mode of information processing in prefrontal cortex, with integration cells situated toward the output of the decision-making process. In these cells, the response to irrelevant information appears as a congruency effect, with better go/no-go discrimination when both the relevant and irrelevant feature are associated with the same response than when they are associated with different responses. This congruency effect could be the result of the combined input from color- and motion-feature cells. Thus these data suggest that irrelevant features lead to partial activation of neurons even toward the output of the decision-making process in primate prefrontal cortex.     

Responses of primate spinothalamic neurons to graded and to repeated noxious heat stimuli.

1. The responses of primate spinothalamic tract cells innervating the glabrous skin of the foot to noxious thermal stimuli have been examined. 2. Of the 41 cells studied, 98% responded to noxious thermal stimuli. Heating the cutaneous receptive field with a series of stimuli from 35 to 43, 47, and 50 degrees C produced a graded increase in discharge rate. The responses were characterized by an onset, which occurred after the temperature change had either slowed or stopped, an acceleration in the discharge up to a peak, and then an adaptation to a new base-line level. The time constants of adaptation were faster than those reported for C polymodal nociceptors. 3. No systematic differences were found in the responses to noxious thermal stimuli of cells with wide dynamic range receptive fields and of cells with narrow dynamic range, high-threshold receptive fields. There were also no differences in the responses of cells located in the marginal zone and of cells located in the neck of the dorsal horn. 4. The relationship between peak frequency and final skin temperature with a 30 s stimulus duration can best be described by a power function with an exponent of 2.1. An increase in the stimulus duration to 120 s resulted in an increase in the exponent of the power function to 3.2. 5. Repetition of the series of 30-s heat stimuli resulted in an increase in peak frequency, total impulse count, and background activity. Repetition of stimuli having a duration of 120 s produced an increase in the peak frequency at 43 and 45 degrees C, a smaller increase at 47 degrees C, and a decrease at 50 degrees C. Background activity was increased by the lower temperature stimuli, but was decreased following higher temperature stimuli. 6. In six additional cells, the skin was heated with three consecutive presentations at each temperature level (43, 45, 47, and 50 degrees C) for 30 s. No change was observed in the peak frequencies of the responses to successive stimuli of the same intensity. However, the exponent of the power function relating the average peak frequency for the six cells to changes in skin temperature was 3.9. This exponent was larger than that seen when two series of graded heat stimuli of 120 s duration were used, indicating more sensitization despite the fact the total time of exposure to noxious heat was less. 7. A role for both high-threshold and wide dynamic range spinothalamic cells in transmitting nociceptive information to the diencephalon is postulated.     

Responses of developing pedunculopontine neurons to glutamate receptor agonists

The pedunculopontine nucleus (PPN) is involved in the generation and maintenance of waking and rapid eye movement (REM) sleep, forming part of the reticular activating system. The PPN receives glutamatergic afferents from other mesopontine nuclei, and glutamatergic input is believed to be involved in the generation of arousal states. We tested the hypothesis that, from postnatal days 9 to 17 in the rat, there are developmental changes in the glutamate receptor subtypes that contribute to the responses of PPN neurons. Whole cell patch-clamp recordings were conducted using brainstem slices from 9- to 17-day-old rats. All cells (types I, II, and III; randomly selected or thalamic-projecting) responded to bath application of the glutamate receptor agonists N-methyl-d-aspartic acid (NMDA) and kainic acid (KA). A developmental decrease in the contribution of the NMDA receptor and developmental increase in the contribution of the KA receptor was observed following electrical stimulation-induced glutamate input. These changes were also observed following bath application in different cell types (randomly selected vs. thalamic-projecting). KA bath application produced an increase in the paired-pulse ratio (PPR) and a decrease in the frequency of miniature excitatory postsynaptic currents (mEPSCs), suggesting that presynaptic KA autoreceptors may decrease the probability of synaptic glutamate input. In contrast, NMDA application produced no changes in the PPR or mEPSCs. Changes in glutamatergic excitability of PPN cell types could underlie the developmental decrease in REM sleep.     

Face-selective and auditory neurons in the primate orbitofrontal cortex

Neurons with responses selective for faces are described in the macaque orbitofrontal cortex. The neurons typically respond 2–13 times more to the best face than to the best non-face stimulus, and have response latencies which are typically in the range of 130–220 ms. Some of these face-selective neurons respond to identity, and others to facial expression. Some of the neurons do not have different responses to different views of a face, which is a useful property of neurons responding to face identity. Other neurons have view-dependent responses, and some respond to moving but not still heads. The neurons with face expression, face movement, or face view-dependent responses would all be useful as part of a system decoding and representing signals important in social interactions. The representation of face identity is also important in social interactions, for it provides some of the information needed in order to make different responses to different individuals. In addition, some orbitofrontal cortex neurons were shown to be tuned to auditory stimuli, including for some neurons, the sound of vocalizations. The findings are relevant to understanding the functions of the primate including human orbitofrontal cortex in normal behaviour, and to understanding the effects of damage to this region in humans.     

Responses of primate spinothalamic tract neurons to renal pelvic distension

1. Experiments were performed to examine responses of spinothalamic tract (STT) neurons to distension of the renal pelvis. Nineteen monkeys (Macaca fascicularis) were anesthetized with alpha-chloralose, paralyzed, and artificially ventilated. Fifty-four STT neurons in the T11-L2 segments were studied. Each cell was excited by renal nerve stimulation and had a somatic receptive field in the left flank and/or the abdomen. 2. Distension of the left renal pelvis to 50 mmHg for 20-30 s increased activity of 40 STT neurons. Two types of responses were observed. Six cells responded rapidly to the increase in renal pelvic pressure. Thereafter activity of these cells completely adapted. The other 34 cells also responded rapidly to the distension: however, the subsequent adaptation was not complete. Average activity before distension was 13 +/- 1 (SE) spikes/s. Distension increased activity to a peak of 42 +/- 3 spikes/s. Mean activity just before the end of the distension was 27 +/- 3 spikes/s. 3. The pelvic pressure-cell response relation was determined for 16 cells. Only one cell responded to a pressure of 20 mmHg. Three responded to 30 mmHg, and all others responded to 40 mmHg and higher. The average response threshold was 32 +/- 1 mmHg. Peak responses increased as distending pressure increased from 40-80 mmHg. Responses to a pressure of 100 mmHg were no greater than to 80 mmHg. Adapted levels of activity were also a function of distending pressure in the 40-80 mmHg range. 4. Probability of responses was unrelated to somatic input. However, cells with A delta- and C-fiber renal input were significantly more likely to respond to renal pelvic distension than cells with only A delta-renal input. Magnitude of responses to a pressure of 50 mmHg was not related to the type of renal input to the cells; however, among the cells tested at all pressures, cells with A delta- and C-fiber input had significantly greater responses to pressures of 80 and 100 mmHg. 5. Cells were studied in laminae I and IV-VII: responses were unrelated to laminar location. None of the 6 cells located in L2 responded to renal pelvic distension; 8 of 12 in L1 responded; 24 of 28 in T12 responded; and all 8 cells in T11 responded. 6. Stimulation of inhibitory receptive fields on the right hindlimb reduced activity of four cells to a significantly greater extent during pelvic distension than before pelvic distension.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses of primate spinothalamic tract neurons to electrical stimulation of hindlimb peripheral nerves.

The responses of spinothalamic tract neurons were studied by extra- and intracellular recordings from the lumbosacral spinal cord in anesthetized rhesus monkeys (Macaca mulatta). The neurons were identified by antidromic activation from the contralateral diencephalon. They were then classified by the mildest form of mechanical stimulation applied to the ipsilateral hindlimb. The effects of electrical stimulation of the nerve(s) supplying the receptive field were investigated. Graded electrical stimulation revealed that the threshold responses of spinothalamic tract neurons excited by weak mechanical stimuli occurred when the largest afferent fibers were activated. On the other hand, neurons that required intense mechanical stimulation for their excitation tended to have higher thresholds to electrical stimulation. Some spinothalamic tract cells were shown to receive monosynaptic excitatory connections from peripheral nerve fibers, although polysynaptic connections may generally be more important. An input from unmyelinated afferent fibers was demonstrated. It is concluded the primate spinothalamic tract neurons receive a rich convergent input from a variety of cutaneous receptors. The experiments provide some evidence for the most likely types of receptors.     

Activity of primate subgenual cingulate cortex neurons is related to sleep

The most frequent type of neuronal response found in the subgenual cingulate cortex (area 25) of the rhesus macaque was a highly significant increase of firing rate when the monkey fell asleep (median rate = 1.6 spikes/s) compared with the awake state (median rate = 0.1 spikes/s). On average, the firing rate of the neurons when awake was 23% of that when the monkeys were asleep. Neurons were not found in this region with responses related to taste, olfactory, and visual stimuli including faces or related to movement. These results are relevant to understanding the function of this region in humans, in which it has been suggested that activation may be related to disengagement from tasks and to induced sadness, both of which we note lead to a more passive or resting behavior. A decrease in the activation of this area in humans has been observed during the recovery from depression, which we note leads to a more active state of behavior.     

Responses of cat vestibular neurons to stimulation of the frontal cortex

Summary To study the neural basis for the regulation of vestibulocollic reflexes during voluntary head movements, the effects of stimulation of the precruciate cortex near the presylvian sulcus (neck area of the motor cortex) and the frontal eye fields (FEF) on vestibular neurons were studied in cerebellectomized cats anesthetized with chloralose. Neurons were recorded in the medial and descending vestibular nuclei and antidromically identified from C₁. Stimulation of the FEF and precruciate cortex fired 29 and 13% of neurons that did not exhibit spontaneous activity. About 80% of spontaneously discharging neurons were influenced by stimulation of either of the two. Stimulation of the precruciate cortex or FEF suppressed or facilitated labyrinthine evoked monosynaptic activation of vestibulospinal neurons, suggesting that the frontal cortical neurons have the properties to regulate the vestibulocollic reflexes.     

Responses of motor cortex neurons to visual stimulation in the alert monkey

Evidence for visually evoked activity in single neurons of area 4 is presented. These neurons modulated their activity in relation to stimuli moving across the visual field of the monkey, without showing habituation. Some of them even had direction sensitivity. Their activity was independent of eye movements and unrelated to muscle contractions. The visually activated neurons were distributed throughout the depth of motor cortex.     

Responses of neurons in the cat primary auditory cortex to sequential sounds

In the natural acoustic environment sounds frequently arrive at the two ears in quick succession. The responses of a cortical neuron to acoustic stimuli can be dramatically altered, usually suppressed, by a preceding sound. The purpose of this study was to determine if the binaural interaction evoked by a preceding sound is involved in subsequent suppressive interactions observed in auditory cortex neurons. Responses of neurons in the primary auditory cortex (AI) exhibiting binaural suppressive interactions (EO/I) were studied in barbiturate-anesthetized cats. For the majority (72.5%) of EO/I neurons studied, the response to a monaural contralateral stimulus was suppressed by a preceding monaural contralateral stimulus, but was not changed by a preceding monaural ipsilateral stimulus. For this subset of EO/I neurons, when a monaural contralateral stimulus was preceded by a binaural stimulus, the level of both the ipsilateral and the contralateral component of the binaural stimulus influenced the response to the subsequent monaural contralateral stimulus. When the contralateral level of the binaural stimulus was constant, increasing its ipsilateral level decreased the suppression of the response to the subsequent monaural contralateral stimulus. When the ipsilateral level of the binaural stimulus was constant, increasing its contralateral level increased the suppression of the response to the subsequent monaural contralateral stimulus. These results demonstrate that the sequential inhibition of responses of AI neurons is a function of the product of a preceding binaural interaction. The magnitude of the response to the contralateral stimulus is related to, but not determined by the magnitude of the response to the preceding binaural stimulus. Possible mechanisms of this sequential interaction are discussed.     

Responses of primate visual cortical V4 neurons to simultaneously presented stimuli

We report here results from 45 primate V4 visual cortical neurons to the preattentive presentations of seven different patterns located in two separate areas of the same receptive field and to combinations of the patterns in the two locations. For many neurons, we could not determine any clear relationship for the responses to two simultaneous stimuli. However, for a substantial fraction of the neurons we found that the firing rate was well modeled as the maximum firing rate of each stimulus presented separately. It has previously been proposed that taking the maximum of the inputs ("MAX" operator) could be a useful operation for neurons in visual cortex, although there has until now been little direct physiological evidence for this hypothesis. Our results here provide direct support for the hypothesis that the MAX operator plays a significant (although certainly not exclusive) role in generating the receptive field properties of visual cortical neurons.     

Dopamine increases excitability of pyramidal neurons in primate prefrontal cortex

Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 (n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 microM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 microM) but not significantly altered by the D2 antagonist sulpiride (2.5 microM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.     

Responses of cat motor cortex neurons to cortico-cortical and somatosensory inputs

Summary Intracellular techniques were used to investigate a cortico-cortical path from sensory cortex to motor cortex of cats. Cortico-cortical epsps were evoked in motor cortex neurons by microstimulation of area 3a. Epsps with latencies between 1.2 and 2.4 ms were identified as monosynaptic. These short latency cortico-cortical effects were recorded in layers II through VI of the motor cortex. Neurons with monosynaptic cortico-cortical epsps also received excitatory inputs from forelimb nerves, usually from both muscle and cutaneous afferent fibers. The epsps evoked from forelimb nerves in motor cortex neurons were preceded by neural activity in somatosensory cortex. Time delays between arrival of inputs in sensory cortex and in motor cortex were compared to the latencies of cortico-cortical epsps in the same motor cortex neurons. It was apparent that the timing was appropriate for the identified cortico-cortical path to have relayed some sensory inputs to motor cortex.Supported by the Medical Research Council of Canada (MT-7373, DG-186), the Harry Botterell Foundation for the Neurological Sciences, the Ontario Ministry of Health, and the Faculty of Medicine, Queen's UniversityRecipient of a Medical Research Council of Canada Studentship.Recipient of a Medical Research Council of Canada Fellowship     

Responses of neurons in the cat posteromedial lateral suprasylvian cortex to moving texture patterns

The posteromedial lateral suprasylvian cortex represents a point of convergence between the geniculostriate and extrageniculostriate visual pathways. Given its purported role in motion analysis and the conflicting reports regarding the texture sensitivity of this area, we have investigated the response properties of cells in PMLS to moving texture patterns ("visual noise"). In contrast to previous reports, we have found that a large majority of cells (80.1%) responds to the motion of a texture pattern with sustained discharges. In general, responses to noise were more broadly tuned for direction compared to gratings; however, direction selectivity appeared more pronounced in response to noise. The majority of cells was selective for drift velocity of the noise pattern (mean optimal velocity: 26.7 degrees /s). Velocity tuning was comparable to that of its principal thalamic input, the lateral posterior pulvinar nucleus. In general, responsiveness of cells in the posteromedial lateral suprasylvian cortex increased with increasing texture element size, although some units were tuned to smaller element sizes than the largest presented. Finally, the magnitude of these noise responses was dependent on the area of the visual field stimulated. In general, a stimulus corresponding to roughly twice the size of the receptive field was required to elicit an equivalent half-maximal response to that for gratings.The results of this study indicate that the majority of cells in the posteromedial lateral suprasylvian cortex can be driven by the motion of a fine texture field, and highlight the importance of this area in motion analysis.