Taste and olfactory modulation of feeding related neurons in behaving monkey.

Single neuron activity in the monkey lateral hypothalamus (LHA) was recorded by multibarreled electrode during a bar press feeding task. Activity of glucose-sensitive (GS) neurons decreased during bar press (BP) and reward (RW) periods. The inhibition was caused by activation of beta-adrenoceptors and opioid receptors respectively. Glucose-insensitive (GIS) neurons were excited during BP and RW, and at cue light (CL). Excitation at CL and BP was caused by activation of dopaminergic receptors. Among GS neurons, 66% responded to taste and 88% to odor. These responses were 39% and 52% in GIS neurons. GS neurons responded predominantly to two or more taste and odor stimuli while GIS neurons responded to only one stimulant. GS neurons have dense mutual connections with the prefrontal area, and GIS neurons are connected with the motor area. Gustatory and olfactory stimulation elicited responses in 67% of GS neurons and in only 21% of GIS neurons. Data suggest that GS and GIS neurons may have different functions in feeding: GS neurons process endogenous chemical information and integrated chemical sensations, and GIS neurons process external information processing, motor control and discriminative chemical sensations.     

Spontaneous activity of the perirhinal cortex in behaving cats.

The perirhinal cortex lies at the interface between the neocortex and allocortex. Whether the perirhinal cortex expresses spontaneous electroencephalographic rhythms that are characteristic of the allocortex and/or of the neocortex is unknown. Thus, the present investigation was undertaken to characterize the activity of the perirhinal cortex with respect to various electroencephalographic rhythms that are displayed by neocortical areas or the entorhino-hippocampal system during different behavioral states of vigilance in chronically-implanted cats. Although perirhinal and neocortical electroencephalograms underwent similar state-dependent changes in amplitude, the ubiquitous neocortical sleep spindles were absent from the perirhinal cortex. In addition, while the slow sleep oscillation (0.5-1 Hz), which is pervasive in the neocortex, was present in the perirhinal cortex, its temporal relation to the neocortical oscillation was highly variable. In contrast, a high degree of correlation was found between perirhinal and entorhinal electroencephalographic activities in all behavioral states. In particular, during waking and paradoxical sleep, multiple simultaneously recorded entorhinal and perirhinal sites displayed an oscillation in the theta range which was highly correlated. To rule out the possibility that the perirhinal theta oscillation reflected volume conduction from neighboring structures, single-unit recordings were performed. Spike-triggered averages and peri-event histograms revealed that perirhinal cells displayed a statistically significant theta-related modulation of their spontaneous activity, albeit weaker than that observed in the entorhinal cortex. Thus, from the standpoint of spontaneous electroencephalographic rhythms, the perirhinal cortex is more closely related to the entorhino-hippocampal system than to the neocortex.     

Increase of spiny I activity in striatum after development of context-dependent sensitization of catalepsy in rats

In this study, it was investigated whether context-dependent sensitization of catalepsy changes the firing pattern in striatum. Rats were treated with either haloperidol (0.5 mg/kg i.p.) or saline, and tested on catalepsy with a concomitant single-unit measurement of the spiny I activity. Administration of haloperidol caused sensitization of catalepsy as measured on bar and grid. Concurrent within this behavioral change, spike-frequency increased over the course of the testing days in haloperidol-treated rats whereas the spike-frequency remained unchanged in saline-treated animals. Burst-frequency remained unchanged within both treatment groups over the days. In conclusion, sensitization of catalepsy is represented by striatal cellular activity as indicated by increases in spike-frequency of spiny I neurons.     

Wireless voltammetry recording in unanesthetised behaving rats

In vivo voltammetry is a valuable technique for rapid measurement of dopamine in the brain of freely behaving rats. Using a conventional voltammetry system, however, behavioural freedom is restricted by cables connecting the head assembly to the measurement system. To overcome these difficulties, we developed a wireless voltammetry system utilizing radio waves. This system consisted of a potentiostat and transmitter system that was mounted on the back of the rat, and a receiver and analysis system. A single-step pulse (100-250 mV) was applied at 4 Hz after an activation pulse to a carbon fibre recording electrode (diameter: 7 microm). Measurement of dopamine (detection limit: 2.7 x 10(-7)M) was demonstrated in vitro. In vivo experiment was performed at least 1 week after the recording electrode was implanted in the rat striatum. Administration of 2-phenylethylamine to rats increased dopamine signal current, which was consistent with the result in the microdialysis measurement. During a resident-intruder test, dopamine signal current in a resident rat increased upon introduction of an intruder rat. These results show that the present wireless system is useful for a long-term measurement of dopamine in behaving rats.     

Multi-unit recordings reveal context-dependent modulation of synchrony in odor-specific neural ensembles

We used neural ensemble recording to examine odor-evoked ensemble patterns in the moth antennal (olfactory) lobe. Different odors are thought to evoke unique spatiotemporal patterns of glomerular activity, but little is known about the population dynamics underlying formation of these patterns. Using a silicon multielectrode array, we observed dynamic network interactions within and between glomeruli. Whereas brief odor pulses repeatedly triggered activity in the same coding ensemble, the temporal pattern of synchronous activity superimposed on the ensemble was neither oscillatory nor odor specific. Rather, synchrony strongly depended on contextual variables such as odor intensity and intermittency. Also, because of emergent inhibitory circuit interactions, odor blends evoked temporal ensemble patterns that could not be predicted from the responses to the individual odorants. Thus even at this early stage of information processing, the timing of odor-evoked neural representations is modulated by key stimulus factors unrelated to the molecular identity of the odor.     

Nucleus accumbens single-unit activity in freely behaving male rats during approach to novel and non-novel estrus

Metabotropic glutamate receptors (mGluRs) were previously shown to mediate a postsynaptic late propagation component elicited by layer Ib stimulation in guinea pig piriform cortex slices. In the present study, the effects of some group specific or subtype specific mGluR antagonists on the late propagation component were investigated using an optical imaging method, in order to identify mGluR subtypes mediating it. A selective mGluR1 antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid most effectively suppressed the late component whereas a selective mGluR5 antagonist, selective group II or group III antagonists showed little or no suppressive effect. These results suggest that the late propagation component is mediated by mGluR1.     

Pharmacological modulation of suppressor cell activity in mice with disseminated histoplasmosis.

Indomethacin and cyclophosphamide (CY) were used in an attempt to modify the suppressive effects of spleen cell populations from mice with disseminated histoplasmosis at 1 week of infection. In vitro addition of indomethacin did not alter the depressed plaque-forming cell response to sheep erythrocytes of normal spleen cells cocultured with unfractionated or nylon wool-fractionated spleen cells from infected mice. Likewise, indomethacin given intraperitoneally did not enhance the subnormal in vivo plaque-forming cell response of spleen cells from infected mice. Conversely, 20 mg of CY per kg given intraperitoneally 2 days before or 6 h after the inoculation with Histoplasma capsulatum partially reversed the suppression effected by splenic T cells (nylon wool passed) in vitro, whereas 50 mg of CY per kg given intraperitoneally 6 h after the injection of H. capsulatum ablated suppressor T cell activity in vitro; neither dosage of CY altered the suppression mediated by unseparated or nylon wool-adherent spleen cells. Furthermore, the administration of 50 mg of CY per kg failed to improve the depressed footpad responses of mice infected for 1 week to sheep erythrocytes in sheep erythrocyte-sensitized mice or to histoplasmin. These findings indicate that in experimental disseminated histoplasmosis, suppression effected by splenic T cells can be alleviated by CY; however, there is a persistent immunosuppressor mechanism(s) that cannot be counteracted by either indomethacin or CY.     

Retinal detector activity in frogs behaving freely

Retinal detector activity was investigated in frogs behaving freely in their natural habitat. On the basis of the experimental results the formation of visually dependent behavior in frogs is explained on the assumption that each type of retinal detector is linked with a particular behavioral response.     

Opioid modulation of magnocellular neurosecretory cell activity

Magnocellular neurosecretory cells of the hypothalamic supraoptic and paraventricular nuclei secrete the hormones, oxytocin and vasopressin, into the systemic circulation from the posterior pituitary gland. Oxytocin is important for parturition and is essential for lactation. Vasopressin regulates body fluid homeostasis. The secretion of these hormones is altered in response to peripheral stimuli that are conveyed via projections from other parts of the brain. Endogenous opioid peptide systems interact with the magnocellular neurosecretory system at several levels to restrain the basal secretion of these hormones as well as their secretory responses to various physiological stimuli. The inhibition of basal secretion can occur at the level of the neurosecretory terminals where endogenous opioids inhibit the release of oxytocin, and at the cell bodies of magnocellular cells to modulate the activity pattern of vasopressin cells. The responses of the magnocellular neurosecretory system to physiological stimuli are also regulated by these mechanisms but in addition probably also by pre-synaptic inhibition of afferent inputs to magnocellular cells as well as direct effects on the cell bodies of afferent input cells to modulate their activity. Here, we review the mechanisms and functional consequences of opioid interactions with oxytocin and vasopressin cells.     

Responses from parabrachial gustatory neurons in behaving rats

1. The responses of a total of 70 single neurons were recorded from the parabrachial nuclei (PBN) in awake rats. In 59 neurons, sapid stimuli (0.5 ml) elicited significant taste responses. Of these 59 neurons, 10 also had significant responses to water. The mean spontaneous rate of the taste neurons was 13.4 +/- 6.9 (SD) spikes/s. Of the remaining 11 neurons, 9 responded significantly only to water; 2 had no significant responses to the standard fluid stimuli. 2. Based on the magnitude of their response to our four standard stimuli, the taste neurons were classified as follows: 42 NaCl-best, 14 sucrose-best, 2 citric acid-best, and 1 QHCl-best. Of these, 25 responded only to one of four sapid stimuli; 20 of these specific cells responded only to NaCl. All the remaining 34 neurons responded to two or more of the four sapid stimuli, with NaCl and sucrose responsiveness dominant. For the 59 taste neurons, the mean entropy for the absolute value of the responses was 0.68; for the excitatory activity alone, it was 0.58. 3. The mean responses to NaCl and sucrose concentration series increased monotonically. Except at the lowest concentration, responses to citric acid also increased monotonically, but with a lower slope. Mean responses to QHCl, however, remained stable or even decreased with increasing concentration. Thus the power functions for the NaCl and sucrose intensity-response series were higher than those of citric acid and QHCl. 4. A hierarchical cluster analysis of 59 parabrachial neurons suggested four different categories: NaCl-best, sucrose-best, citric acid-best, and QHCl-best. These categories were less evident in the two-dimensional space produced by multidimensional analysis, because the positions of NaCl- and sucrose-best neurons formed a continuum in which neural response profiles change successively from sucrose-specific to NaCl-specific. 5. The results were consistent with previous anatomic and neurophysiological data suggesting convergence in the medulla of sensory input from receptors in the nasoincisor ducts (NID) and on the anterior tongue (AT). Taste buds in the NID respond preferentially to sucrose, whereas those on the AT respond more to NaCl.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pulvinar nuclei of the behaving rhesus monkey: visual responses and their modulation

We have examined the properties of neurons in three subdivisions of the pulvinar of alert, trained rhesus monkeys 1) an inferior, retinotopically mapped area (PI), 2) a lateral, retinotopically organized region (PL), and 3) a dorsomedial visual portion of the lateral pulvinar (Pdm), which has a crude retinotopic organization. We tested the neurons for visual responses to stationary and moving stimuli and for changes in these responses produced by behavioral manipulations. All areas contain cells sensitive to stimulus orientation as well as neurons selective for the direction of stimulus movement; however, the majority of cells in all three regions are either broadly tuned or nonselective for these attributes. Nearly all cells respond to stimulus onset, a significant number also give a response to stimulus termination, and rarely a cell gives only off responses. Nearly all cells increase their discharge rate to visual stimuli. Receptive fields in the two retinotopically mapped regions, PI and PL, have well-defined borders. The sizes of these receptive fields show a positive correlation with the eccentricity of the receptive fields. The receptive fields in the remaining region, Pdm, are frequently very large, but with these large fields excluded, show a similar correlation with eccentricity. All pulvinar cells tested (n = 20) were mapped in retinal coordinates; the receptive fields are positioned in relation to the retina. We found no cells with gaze-gated characteristics (2), nor cells mapped in a spatial coordinate system. The response latencies in PI and PL are shorter and less variable than the latencies in Pdm. Active use of a stimulus can produce an enhancement or attenuation of the visual response. Eye-movement modulation was found in all three subdivisions in about equal frequencies. Attentional modulation was common in Pdm and was rare in PI and PL. The modulation is spatially selective in Pdm and nonselective in PI for a small number of tested cells. These data demonstrate functional differences between Pdm and the other two areas and suggest that Pdm plays a role in selective visual attention, whereas PI and PL probably contribute to other aspects of visual perception.     

Gustatory responses of neurons in the nucleus of the solitary tract of behaving rats.

1. The activity of 117 single neurons was recorded in the rostral nucleus of the solitary tract (NST) and tested with each of four standard chemical stimuli [sucrose, NaCl, citric acid, and quinine HCl (QHCl)] and distilled water in awake, behaving rats. In 101 of these neurons, at least one sapid stimulus elicited a significant taste response. The mean spontaneous rate of the taste neurons was 4.1 +/- 5.8 (SD) spike/s. The mean response magnitudes were as follows: sucrose, 10.6 +/- 11.7; NaCl, 8.6 +/- 14.6; citric acid, 6.2 +/- 7.8; and QHCl, 2.4 +/- 6.6 spikes/s. 2. On the basis of their largest response, 42 taste neurons were classified as sucrose-best, 25 as NaCl-best, 30 as citric acid-best, and 4 as QHCl-best. The mean spontaneous rates for these categories were 4.9 +/- 6.2 for sucrose-best cells, 5.8 +/- 7.4 for NaCl-best, 1.6 +/- 2.0 for citric acid-best, and 5.8 +/- 6.0 spikes/s for QHCl-best. The spontaneous rate of the citric acid-best neurons was significantly lower than that of the other categories. 3. At the standard concentrations, 45 taste cells (44.6%) responded significantly to only one of the gustatory stimuli. Of the 30 acid-best neurons, 23 (76.7%) responded only to citric acid. For sucrose-best cells, specific sensitivity was less common (18/42, 42.9%), and for NaCl-best neurons, it was relatively uncommon (3/25, 12%). One of the 4 QHCl-best neurons was specific. In a concentration series, more than one-half of the 19 specific neurons tested responded to only one chemical at any strength. 4. The mean entropy for the excitatory responses of all gustatory neurons was 0.60. Citric acid-best cells showed the least breadth of responsiveness (0.49), sucrose-best cells were somewhat broader (0.56), but NaCl-best and QHCl-best cells were considerably less selective (0.77 and 0.79, respectively). Inhibition was observed infrequently and never reached the criterion for significance. 5. In the hierarchical cluster analysis, the four largest clusters segregated neurons primarily by best-stimulus category. The major exception to this was a group of sucrose-best neurons that also responded to NaCl and were grouped with the NaCl-best neurons. In a two-dimensional space, the specific taste neurons, those that responded to only one of the four standard sapid stimuli, remained in well-separated groups. These specific groups, however, were joined in a ring-like formation by other neurons that responded to more than one of the sapid stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)     

In vivo analysis of proprioceptive coding and its antidromic modulation in the freely behaving crayfish

Although sensory nerves in vitro are known to convey both orthodromic (sensory) and antidromic (putatively modulating) action potentials, in most cases very little is known about their bidirectional characteristics in intact animals. Here, we have investigated both the sensory coding properties and antidromic discharges that occur during real walking in the freely behaving crayfish. The activity of the sensory nerve innervating the proprioceptor CBCO, a chordotonal organ that monitors both angular movement and position of the coxo-basipodite (CB) joint, which is implicated in vertical leg movements, was recorded chronically along with the electromyographic activity of the muscles that control CB joint movements. Two wire electrodes placed on the sensory nerve were used to discriminate orthodromic from antidromic action potentials and thus allowed for analysis of both sensory coding and antidromic discharges. A distinction is proposed between 3 main classes of sensory neuron, according to their firing in relation to levator muscle activity during free walking. In parallel, we describe 2 types of antidromic activity: one produced exclusively during motor activity and a second produced both during and in the absence of motor activity. A negative correlation was found between the activity of sensory neurons in each of the 3 classes and identified antidromic discharges during walking. Finally, a state-dependent plasticity of CBCO nerve activity has been found by which the distribution of sensory orthodromic and antidromic activity changes with the physiological state of the biomechanical apparatus.     

Intracellular location and cell context-dependent function of protein kinase D

Protein kinase D (PKD) is an antigen receptor-activated serine kinase localized at either the plasma membrane or the cytosol of lymphocytes. To probe PKD function at these different locations, transgenesis was used to target active PKD either to the membrane or cytosol of pre-T cells. In recombinase gene null pre-T cells, membrane and cytosolic active PKD both induced differentiation reminiscent of beta selection: downregulation of CD25 and upregulation of CD2 and CD5. Active PKDs also induced pre-T cell proliferation, although this response was not universal to all thymocyte subsets. There were two striking differences between the actions of the differentially localized PKDs. Membrane but not cytosolic PKD could induce expression of CD8 and CD4 in recombinase null mice; cytosolic but not membrane PKD suppressed Vbeta to DJbeta rearrangements of the TCRbeta chain locus in wild-type T cells. PKD function is thus determined by its intracellular location and cell context.     

Short-term modulation of cerebellar Purkinje cell activity after spontaneous climbing fiber input.

1. There are two opposite points of view concerning the way climbing fiber input in a Purkinje cell modifies simple spike (SS) activity transiently: depression versus enhancement of SS activity. The different groups of investigators favored one effect predominating over the other. In the decerebrate unanesthetized cat, we recorded spontaneous activity of single Purkinje cells and investigated time course of SS activity after the complex spike (CS). 2. In the peri-CS time histogram, there was a SS pause lasting, on average, 10.8 ms after onset of the CS in all of the 316 cells recorded. The pause was followed by a rapid increase in SS activity to a maximum, which was on average 175.6% of a pre-CS control level, and a gradual return to around the control level in the majority of the cells recorded (pause-facilitation type, 71.2%). The increase in SS activity was significant (P < 0.01, t test) during 20-100 ms. The SS activity during the 20-100 ms was, on average, 163.7% of the control level. In some cells (pure-pause type, 25.3%), no significant changes were found (P > 0.01) in the post-pause SS firing. In contrast, only 3.5% of the cells (pause-reduction type) showed a significant (P < 0.01) firing decrease (average 54.0% of the control level) lasting 20-60 ms after the pause period. 3. Analysis of the pre-CS time histogram revealed no significant differences (P > 0.01) in the SS activity between pre-CS periods in all of the cells recorded, suggesting that the SS activity enhancement is not due to a coactivated mossy fiber input just preceding the activation of the climbing fiber input. 4. Analysis of the raster diagram revealed variability of individual SS responses after the CS. The probability of occurrence of the increase in SS number during a post-CS period of 0-100 ms with respect to that during a pre-CS period of -100-0 ms in individual raster traces was high (on average 78.2%), medium (57.3%), and low (36.3%) in the pause-facilitation, pure-pause, and pause-reduction types of the cell, respectively. 5. Nonsequential time histograms showing frequency distribution of the pause duration after the CS in individual raster traces and that showing interspike intervals of the SS were constructed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Narcotic-induced suppression of natural killer cell activity in ventilated and nonventilated rats.

Surgical stress and general anesthesia can suppress immune function and thus may increase postsurgical infections and tumor metastasis. We previously reported that two narcotics commonly used in high-dose opiate anesthesia (fentanyl and sufentanil) suppress natural killer (NK) cell activity in rats. Such doses of narcotics also cause respiratory depression accompanied by hypoxia, hypercarbia, and acidosis, which might account for the observed narcotic-induced NK suppression. In the present study, we compared the effects of fentanyl on NK activity in ventilated and non-ventilated rats. Fentanyl significantly suppressed NK cell activity to the same magnitude in the two groups, although the groups significantly differed in CO2 and O2 levels. The fact that high-dose fentanyl-induced NK suppression can be demonstrated in ventilated rats accentuates the relevance of these findings to clinical studies showing NK suppression in the immediate postoperative period. Such immunosuppression could be a risk factor for patients undergoing surgery, especially in cancer-related operations.     

The orbitofrontal cortex: Neuronal activity in the behaving monkey

Summary Single unit recording of neurons in the orbitofrontal cortex of the alert rhesus monkey was used to investigate responses to sensory stimulation. 32.4% of the neurons had visual responses that had typical latencies of 100–200 ms, and 9.4% responded to gustatory inputs. Most neurons were selective, in that they responded consistently to some stimuli such as foods or aversive objects, but not to others. In a number of cases the neurons responded selectively to particular foods or aversive stimuli. However, this high selectivity could not be explained by simple sensory features of the stimulus, since the responses of some neurons could be readily reversed if the meaning of the stimulus (i.e. whether it was food or aversive) was changed, even though its physical appearance remained identical. Further, some bimodal neurons received convergent visual and gustatory inputs, with matching selectivity for the same stimulus in both modalities, again suggesting that an explanation in terms of simple sensory features is inadequate.Neurons were also studied during the performance of tasks known to be disrupted by orbitofrontal lesions, including a go/no go visual discrimination task and its reversal. 8.6% of neurons had differential responses to the two discriminative stimuli in the task, one of which indicated that reward was available and the other saline. Reversing the meaning of the two stimuli showed that whereas some differential units were closely linked to the sensory features of the stimuli, and some to their behavioural significance, others were conditional, in that they would only respond if a particular stimulus was present, and if it was the one being currently rewarded. Other neurons had activity related to the outcome of the animal's response, with some indicating that reinforcement had been received and others, that an error had been made and that a reversal was required.Thus, neurons in the orbitofrontal cortex possess highly coded information about which stimuli are present, as well as information about the consequences of the animal's own responses. It is suggested that together they may constitute a neuronal mechanism for determining whether particular visual stimuli continue to be associated with reinforcement, as well as providing for the modification of the animal's behavioural responses to such stimuli when those responses are no longer appropriate.