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S L Foote

Publications and source records attributed to S L Foote.

At least 19 recordsLinked to original sources
PubMed1992

Distribution of corticotropin-releasing factor-like immunoreactivity in squirrel monkey (Saimiri sciureus) amygdala.

Previous anatomical studies of corticotropin-releasing factor (CRF)-like immunoreactivity in rat brain have reported prominent clustering of neuronal elements containing this peptide within the amygdala. The highest concentrations of both CRF-positive cells and fibers were evident in the central nucleus, an observation consistent with the putative role of this peptide in autonomic and endocrine regulation. In addition, lower densities of CRF-positive somata and processes have been noted in other amygdaloid nuclei. However, the distribution of CRF-like immunoreactivity in the amygdala has not been described for any primate species. Such a description would be of interest since substantial differences in the distribution of CRF in rodent and primate have been reported for other brain regions. The present study uses immunohistochemical methods, with a polyclonal antiserum directed against the human form of CRF, to determine the distribution of this peptide in non-colchicine-treated monkeys (Saimiri sciureus). Within the amygdaloid complex, the most numerous and concentrated collections of CRF-positive neurons were seen in the basal and lateral nuclei. The highest densities of CRF-positive fibers and terminals were seen in the lateral and central amygdaloid nuclei. Moderately dense plexuses of CRF-positive fibers also were seen in layer Ia of the periamygdaloid cortex, nucleus of the lateral olfactory tract, anterior and posterior cortical nuclei, and the medial nucleus. Thus, the distribution of CRF-like immunoreactivity differs substantially in monkey and rat amygdala. Since CRF-positive perikarya in monkey are most prominent in nuclei with pronounced interconnections with neocortex, these differences may be an integral component of the increased cortical development that characterizes the primate brain.

Amygdala↗
PubMed1992

Localization of corticotropin-releasing factor-like immunoreactivity in monkey olfactory bulb and secondary olfactory areas.

Electrophysiological and anatomical observations suggest that terminals of olfactory bulb mitral cells ending in rat primary olfactory cortex exert certain postsynaptic effects via an excitatory amino acid neurotransmitter. Recent anatomical studies have shown that several peptides, most notably corticotropin-releasing factor (CRF) (Imaki et al., '89) Brain Res., 496: 35-44), are also localized within rat olfactory bulb projection neurons, thus raising the possibility that there is a peptide cotransmitter in this system. In contrast to the availability of data for rodents, very little is known about the distribution of peptides and other putative transmitters in the olfactory systems of primate species. In the present study, sections through the olfactory bulb and its target areas were obtained from two monkey species (Saimiri sciureus and Macaca fascicularis) and processed for immunohistochemistry with a well-characterized polyclonal antiserum directed against the human form of CRF. Virtually identical results were obtained in the two species. Within the olfactory bulb, nearly all mitral and many tufted cells contained CRF-like immunoreactivity. CRF-positive fibers were seen within the olfactory tract and olfactory stria, which contain the axons of mitral and tufted cells. Within the anterior olfactory nucleus and layer Ia of the olfactory tubercle and piriform cortex, immunoreactivity was seen within fine processes, as well as in coarse, varicose fibers and isolated puncta. CRF-positive cells were seen within layer III of the olfactory tubercle and piriform cortex. Immunoreactive fibers and varicosities were also seen within olfactory-recipient regions of the amygdala and entorhinal cortex. These observations suggest that CRF may act as a transmitter and/or neuromodulator in primate olfactory system.

Amygdala↗
PubMed1992

Oscillation of interspike interval length in substantia nigra dopamine neurons: effects of nicotine and the dopaminergic D2 agonist LY 163502 on electrophysiological activity.

The rates and patterns of discharge activity exhibited by 16 spontaneously active substantia nigra pars compacta dopamine neurons were studied in halothane-anesthetized rats using three types of quantitative measures: 1) mean discharge rates, 2) population characteristics of interspike interval samples, and 3) interspike interval time-series measures which were used to examine patterns in the ordering of interspike intervals. The mean discharge rate of these 16 cells was 2.9 +/- 0.3 spikes/sec, and each cell was classified as bursting (25% of the cells) or non-bursting (75%). The distribution of interspike intervals of non-bursting neurons were more normally distributed. Time-series analyses (raw time-series plots, return maps, and phase portraits) revealed a substantial oscillatory tendency in the magnitudes of consecutive interspike intervals in these neurons under baseline conditions: Successive interspike intervals tended to alternate between short and long durations, although short bursts often occurred. Under baseline conditions, these cells exhibited both multispike bursts and consecutive long intervals less frequently than would have been predicted by chance ordering of the interspike intervals. These results imply that there are mechanisms acting to reduce the probability of these types of events. Locally infused nicotine enhanced discharge rates in these neurons. Burst firing increased in four neurons, while five neurons did not show any change in burst firing. LY 163502 induced significant decreases in both discharge rate and bursting activity in all cells tested. The variation coefficient, skew, and kurtosis of the interspike interval distributions were not consistently altered by either drug. The local infusion of either nicotine or LY 163502 decreased the oscillatory phenomenon seen in the baseline condition. Neither the nicotine or LY 163502 time-series data exhibited a larger proportion of long-short and short-long pairs (relative to the median interval) than would be expected by chance. It is hypothesized that these neurons have intrinsic mechanisms, made manifest under anesthesia, which induce oscillations in interspike interval length. The oscillatory effect of these mechanisms can be overridden by tonic increases in either excitatory or inhibitory tone.

Anesthesia↗
PubMed1991

Intensity-amplitude relationships in monkey event-related potentials: parallels to human augmenting-reducing responses.

In human, the amplitudes of specific event-related potential (ERP) components can increase or decrease in response to increasing stimulus intensity depending on the location of the recording site. Large increases characterize components presumably generated by modality-specific sites, while smaller increases or even decreases are associated with those originating in associational areas. Comparable data from non-human primates, which would permit invasive studies of the neural substrates underlying these intensity-amplitude differences, are limited. To more fully characterize these relationships, auditory ERPs were recorded from chronically implanted epidural electrodes in 5 squirrel monkeys (Saimiri sciureus) in response to tones (500 Hz, 300 msec duration) of varying intensities (50, 60, 70, 80 dB SPL). Squirrel monkey ERPs recorded at Fz exhibited 3 peaks during the 200 msec post-stimulus interval. These peaks included a positivity (P1), followed by a negativity (N1), and then another positivity (P2). At posterior sites, the frontal P1-N1 configuration was recorded as an N1-P1 complex. At these sites, a small negativity (N2) preceded the last positive peak (P2). Changes in polarity were independent of reference site and posterior N1-P1 peaks exhibited latencies similar to those of the frontal P1-N1 components. Amplitudes at Fz, Cz, and Pz increased substantially with increasing stimulus intensity ('augmenting'). In contrast, only small increases or even decreases in amplitude ('reducing') were evident at T3 and T4. On the other hand, peak latencies decreased with higher stimulus intensities at most sites. The site-specific amplitude responses exhibited considerable temporal stability. In one subject, for example, similar 'augmenting' profiles were recorded at Fz in 8 sessions over a 6-month period. The topography of monkey intensity-amplitude response profiles, their temporal stability, and peak latency shifts resemble observations made in humans. The data show that 'augmenting' characterizes monkey vertex potentials, which, like the analogous human potentials, may originate in primary auditory cortex. In contrast, potentials recorded over temporal cortex, which may originate in auditory association cortex, exhibit 'reducing.' Thus, the data support the hypothesis that differences in amplitude with increasing intensity may reflect differences in cortical origin.

Acoustic Stimulation↗
PubMed1991

Electrophysiological evidence for the involvement of the locus coeruleus in alerting, orienting, and attending.

In this chapter, we describe recent observations from our laboratory which support the thesis that the locus coeruleus (LC), via its massively divergent efferent projections, participates in generating a generalized brain state that can be characterized as "alertness." The first of these observations suggests that LC activation can convert the electroencephalographic (EEG) activity of the forebrain from patterns characteristic of a non-alert state to those characteristic of an alert state. The second observation indicates that LC activation alters sensory responses of individual neocortical neurons in a way that is compatible with the general thesis presented here, suggesting that LC-induced alterations in cortical neuronal activity may be an integral component of a hypothesized participation of the LC in cortically mediated attentional processes. The third observation indicates that LC may modulate forebrain components of orienting responses that are indexed by event-related potentials (ERPs). Thus, the experiments described below involve electrophysiological assessment of forebrain information processing at three different levels of organization: activity of individual neurons in the millisecond range, neuronal ensemble activity persisting for 10-200 msec as indexed by ERPs, and ensemble/regional activity sustained for seconds to minutes as indicated by EEG measures. These observations suggest that alterations induced in forebrain function by manipulations of LC activity are evident at all three of these levels.

Animals↗
PubMed1991

Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus.

Experiments were conducted to examine the hypothesis that increased neuronal discharge activity of noradrenergic neurons of the locus coeruleus (LC) above resting discharge rates can alter forebrain electroencephalographic (EEG) activity. Small infusions (70-135 nl) of the cholinergic agonist bethanechol within 500 microns of the LC were used to activate this nucleus reversibly in halothane-anesthetized rats. A combined recording-infusion probe allowed verification of this electrophysiological activation. Simultaneously, EEG activity was recorded from sites in the frontal cortex and hippocampus and subjected to power-spectrum analyses. The findings were (1) LC activation was consistently followed, within 5 to 30 sec, by a shift from low-frequency, high-amplitude to high-frequency, low-amplitude EEG activity in frontal neocortex and by the appearance of intense theta-rhythm in the hippocampus; (2) forebrain EEG changes followed LC activation with similar latencies whether infusions were made lateral or medial to the LC; (3) infusions placed outside the immediate vicinity of the LC were not followed by these forebrain EEG effects; (4) following infusion-induced activation, forebrain EEG returned to preinfusion patterns with about the same time course as the recovery of LC activity (10-20 min for complete recovery). These infusion-induced effects on EEG activity were blocked or severely attenuated by pretreatment with the alpha 2-agonist clonidine, which inhibits LC discharge and norepinephrine release, or the beta-antagonist propranolol. These observations indicate that enhanced LC discharge activity is the crucial mediating event for the infusion-induced changes in forebrain EEG activity observed under these conditions and suggest that LC activation may be sufficient to induce EEG signs of cortical and hippocampal activation.

Animals↗
PubMed1989

Corticotropin-releasing factor immunoreactivity in monkey neocortex: an immunohistochemical analysis.

Corticotropin-releasing factor (CRF) has been implicated in the pathophysiology of certain human neuropsychiatric disorders that affect neocortical function. However, the anatomical organization of CRF-containing structures in the expanded and highly differentiated primate neocortex has not been previously described. In this study, the distribution of CRF-immunoreactive neurons and processes was characterized in the neocortex of New World squirrel monkeys (Saimiri sciureus). Substantial regional differences were present in the density, laminar distribution, and morphological appearance of CRF-immunoreactive neurons. The greatest density of labeled neurons was present in anterior cingulate cortex. A wide range of intermediate densities of CRF-immunoreactive neurons was evident in the association regions of the prefrontal, parietal, and temporal cortices. The lowest numbers of CRF-immunoreactive neurons were observed in the primary visual and primary motor cortices. For example, the density of labeled neurons was nearly five times greater in the anterior cingulate cortex than in the precentral cortex. CRF-immunoreactive neurons were also distributed in at least four different laminar patterns. For example, in the agranular anterior cingulate cortex, labeled cell bodies were distributed throughout layers II, III, and V. In other regions, such as the posterior cingulate cortex, labeled neurons were present in layers II, III, and IV. In contrast, labeled neurons were predominantly present in layers II and superficial III of the visual cortex, whereas in the inferior temporal cortex, they were present predominantly in layer IV. Regional and laminar differences were also present in the relative distributions of the two major morphological types (as defined by cell body shape) of CRF-immunoreactive neurons. Vertically oriented oval neurons, which frequently had a single dendritic process arising from each somal pole, were most frequently found in layer III. In contrast, the labeled neurons in layers II and IV tended to have a round- or triangular-shaped soma. In layer IV of some association cortices, these multipolar neurons were associated with a high density of rod-like structures composed of large immunoreactive varicosities clustered together in vertical arrays. These structures were frequently found to be located immediately below the soma of pyramidal neurons. Comparison of these findings with Golgi impregnation studies strongly suggests that CRF is present in the soma and axonal cartridges of a subset of chandelier neurons. The heterogeneous distribution and morphological diversity of CRF-containing neurons suggest that CRF may mediate distinct functions in different regions and layers of monkey neocortex.

Animals↗
PubMed1989

Brain-stem auditory evoked potentials in squirrel monkey (Saimiri sciureus).

To more fully characterize brain-stem auditory evoked potentials (BAEPs) in non-human primates, BAEPs were recorded from chronically implanted epidural electrodes in 10 squirrel monkeys (Saimiri sciureus). The effects of stimulus intensity, repetition rate, and anesthesia (ketamine 20 mg/kg i.m.) on peak latencies and inter-peak intervals were evaluated. Monkey wave forms consisted of approximately 7 peaks (I-VII), each exhibiting similar latencies across sessions, with later peaks exhibiting greater variability. In some subjects, additional peaks (IIa, IIIa) and slow potentials were recorded. The slow potentials provided a substratum for peaks IV through VII. As with human, monkey peaks exhibited systematic changes in latency with changes in stimulus intensity or repetition rate. These shifts included significant decreases in latency with increasing intensity for peaks I-IV and increases in latency with increases in repetition rate for peaks III, V, and VI. Inter-peak intervals were similar to those observed in human. Furthermore, ketamine anesthesia significantly delayed the latencies of most peaks (except I, V, and VII). Some differences between monkey and human BAEPs were evident in the relative amplitude of specific peaks. For example, peak V is typically most prominent in human, while this was true for peak III in monkey. The similarities between unanesthetized monkey and human inter-peak intervals suggest that the times required for impulses to reach particular brain-stem areas are conserved across primate species that vary in brain size. This supports the hypothesis that comparably numbered BAEP peaks in monkey and human index homologous processes. The data also suggest that the differences between animal and human BAEPs commonly reported may result from the use of anesthetics. In summary, unanesthetized monkey BAEPs resemble human BAEPs in morphology, number of peaks, polarity, latency variability, inter-peak intervals, slow potentials superimposed on the high-frequency peaks, and variations in morphology, amplitude, and resolution of peaks as a function of recording site. Thus, unanesthetized monkey BAEPs may be an excellent model for investigating the neural substrates of human BAEP or for determining species differences in acoustic processing among primates.

Anesthesia↗
PubMed1989

Effects of locus coeruleus lesions on auditory, long-latency, event-related potentials in monkey.

It has previously been demonstrated that monkeys exhibit certain event-related potential (ERP) components showing latency, polarity, and contingency similarities to those observed in humans. In the present study, monkey P300-like components were studied in order to evaluate the hypothesis that the noradrenergic locus coeruleus (LC) system participates in their generation or modulation. ERPs were recorded from untrained squirrel monkeys (Saimiri sciureus) twice a week for 4 weeks before and after bilateral LC lesions and interruption of dorsal bundle (DB) fibers. Stimuli consisted of 2 and 6 kHz tone pips (40 msec duration, 60 dB above nHL) presented once a second in random order. In most sessions, one tone constituted 90% of the stimuli and the other tone 10%, while in some sessions tones were made equiprobable to test the effects of manipulating stimulus probability. LC and DB lesions were made by first localizing the nucleus and creating an electrolytic lesion. Then, the electrode was placed at the anterior pole of the nucleus and a knife cut effected. The extent of damage to LC perikarya and ascending axons was assessed by reconstructing lesions from Nissl-stained sagittal sections through the brain stems. The effect of lesions on cortical noradrenergic axons was immunohistochemically verified utilizing antisera directed against dopamine-B-hydroxylase and tyrosine hydroxylase to label noradrenergic and dopaminergic axons, respectively. The prelesion ERP results replicated previous findings of P300-like components recorded in response to low-probability tones. The postlesion ERP data indicated that following damage to LC cell bodies, combined with interruption of histochemically detectable ascending noradrenergic axons, monkey P300-like potentials exhibited decreased areas, altered brain-surface distribution, and reduced sensitivity to stimulus probability. The correlation between the extent of cell body lesions and percentage reduction in the magnitude of P300-like responses was significant. However, interruption of DB fibers alone did not have similar effects. Neither type of lesion had any effect on amplitudes, latencies, or brain-surface distributions of P52, P172, or N250-900. There was, however, a significant effect on N106. Stimulus probability effects on the frontally distributed P52 and N106 were not altered by the lesions. These data support the hypothesis that the integrity of the LC nucleus and its ascending fibers is important in the generation and modulation of surface-recorded P300-like activity.

Animals↗
PubMed1988

Distribution of corticotropin-releasing-factor-like immunoreactivity in brainstem of two monkey species (Saimiri sciureus and Macaca fascicularis): an immunohistochemical study.

Immunohistochemical methods were utilized to systematically map the distribution of corticotropin-releasing-factor-like immunoreactivity (CRF-LI) in the diencephalon, mesencephalon, and rhombencephalon of two monkey species (Saimiri sciureus and Macaca fascicularis). A primary antiserum directed against the human form of the peptide was utilized. Immunoreactive neuronal perikarya and processes were evident in numerous areas, and the distributions of these elements were similar for the two species. As previously reported for rats, monkeys, and human, intense immunoreactivity was evident in putative hypophyseal neurons in the parvicellular component of the paraventricular nucleus of the hypothalamus and in fibers extending from this area into the median eminence. The results for other brainstem regions, most of which have been previously examined for CRF-LI only in rats, indicate that many similarities exist between rats and monkeys in the distribution of this peptide in brainstem extrahypophyseal neuronal circuits, although substantial differences are also evident. For example, immunoreactive perikarya previously observed in other hypothalamic nuclei in rats were not evident in monkeys. Conversely, in monkeys, unlike rats, labeled perikarya were evident in several thalamic nuclei, especially in the intralaminar complex. Also, two large groups of immunoreactive neurons which have generally not been observed in rat studies were present in the mesencephalon and rhombencephalon. In the mesencephalon this consisted of a group of neurons just lateral to the mesencephalic tegmentum, extending throughout the rostral-caudal extent of the midbrain. In the rhombencephalon, labeled perikarya were observed throughout the inferior olive. Some of the differences between rats and monkeys in the locations of labeled perikarya may be due to differences in antiserum specificity and/or sensitivity, or they may result from the fact that colchicine pretreatment was not utilized in the present study. The distributions of immunoreactive fibers also exhibited similarities and differences between monkeys and rats. The most striking terminal fields observed in the present study which have not been previously described are a moderate-to-dense field within and adjacent to presumed dopamine-containing neurons in the substantia nigra pars compacta, a dense innervation of certain subdivisions of the interpeduncular nucleus, and a regionally and parasagittally organized distribution of fibers in the Purkinje cell and molecular layers of the cerebellar cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

The dopaminergic innervation of monkey prefrontal cortex: a tyrosine hydroxylase immunohistochemical study.

The distribution of tyrosine hydroxylase (TH)-immunoreactive fibers was characterized immunohistochemically in the prefrontal cortical regions of both Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). In both species, differences in the density and/or laminar distribution of TH-labeled fibers were detected both across and within almost every prefrontal cytoarchitectonic region. In cynomolgus monkeys, areas 9 and 24 had the greatest density of TH-labeled fibers, areas 11, 12, 13 and 25 were of intermediate density, and areas 10 and 46 had the lowest density of immunoreactive fibers. Differences in fiber density within many of these regions were also consistently observed. On a laminar basis, the distribution of labeled fibers in a given area of cynomolgus prefrontal cortex was systematically related to the overall fiber density of that area. For example, in the lightly innervated fundus of the principal sulcus (area 46), labeled fibers were primarily present in layer I and layers V-VI, whereas in area 9, the most densely innervated region, TH-labeled fibers were present in all cortical layers. Similar regional differences in the density and laminar distribution of TH-immunoreactive fibers were also present in squirrel monkey prefrontal cortex. In previous studies, we have analyzed the regional and laminar distributions of fibers immunoreactive for TH and dopamine-beta-hydroxylase (DBH), a specific marker for noradrenergic cortical fibers, in multiple areas of cortex from both normal and locus ceruleus-lesioned animals. These comparisons, which have been confirmed in the present report, indicate that anti-TH and anti-DBH label distinct populations of axons in monkey neocortex, which presumably are dopaminergic and noradrenergic, respectively. Thus, the distribution of TH immunoreactivity described in the present report suggests that dopaminergic fibers are distributed in a very heterogeneous fashion in monkey prefrontal cortex. The distinctive innervation patterns exhibited by these fibers reveal the regions and layers that may be the principle sites of action of dopamine in exerting its effects on prefrontal cortical function.

Animals↗
PubMed1988

Endogenous event-related potentials in monkey: the role of task relevance, stimulus probability, and behavioral response.

Monkeys were trained in auditory discrimination tasks resembling human paradigms in which long-latency endogenous components, such as P300, are typically recorded. Morphological, topographical, and functional properties of the monkey event-related potentials (ERPs) were analyzed to determine similarities and differences with human ERPs reported in the literature. ERPs were recorded from epidural electrodes in monkeys trained to produce operant responses. In a conditional discrimination (CD) task, tone pips (2 kHz or 6 kHz, 40 msec duration, and 60 dB above nHL) were presented every 4-8 sec. Target tones presented during 'time-in' (TI) were rewarded when followed by a response in the correct post-stimulus interval (400-3000 msec). In contrast, tones presented during 'time-out' (TO) were not rewarded. Under both conditions, tones elicited an initial frontally dominant triphasic complex (P56-N92-P157). Additionally, TI target tones followed by a response elicited a large negativity (N358) having maximal amplitude over mid-frontal regions and followed by a parietally distributed positivity (P658). The scalp distribution and covariation with task requirements of N358 resemble those reported for the human 'O' wave. ERPs were also recorded in an auditory oddball paradigm in which tone pips (2 kHz and 6 kHz, 40 msec duration, and 60 dB above nHL) were presented in random order every second. Monkeys trained in the CD paradigm, along with additional subjects, were trained to make delayed responses following target tones embedded in a background of different-pitch tones. Tone probabilities were varied in different sessions from 90-10, 70-30, to 50-50 to assess the effects of probability. Background and target tones elicited a triphasic complex (P52-N110-P159) similar in latency and distribution to that recorded in the CD task. Additionally, target tones in this paradigm elicited a long-latency positive component (LPC) that exhibited an inverse relationship with stimulus probability. LPC had an onset latency of approximately 150-200 msec, a duration of approximately 300 msec, and multiple peaks (P244 and P376). These data indicate the importance of stimulus context in eliciting long-latency endogenous activity. It further suggests that strong analogies exist between monkey and human potentials recorded under similar paradigms. The effects of task relevance, stimulus probability, and the act of producing behavioral responses are similar to the effects of these variables on analogous human potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1988

Effects of locally infused pharmacological agents on spontaneous and sensory-evoked activity of locus coeruleus neurons.

Electrophysiological activity of individual locus coeruleus (LC) neurons was recorded in halothane-anesthetized rats before, during, and after the infusion of adrenergic, cholinergic, or peptidergic compounds about 400 micron lateral to LC. The alpha-adrenergic agonist clonidine (CLON), in concentrations ranging from 5-20 microM (67-270 pg/50 nl injection), reversibly suppressed activity with latencies to onset of 5-15 min and durations of 20-120 min. During the onset of suppressed firing, responses to sensory stimuli (footshock) were relatively preserved, but at later times the reliability of footshock responses was greatly reduced. The alpha-adrenergic antagonist piperoxane (PIP) rapidly reversed the inhibitory effects of CLON. Infusion of 0.1 microliter of 0.02 M acetylcholine (ACh) produced a 3-4 min period of increased LC firing, with a 1 min latency to onset. Larger volumes (0.15 microliter) produced greater increases in firing rate lasting 10-12 min. ACh effects were readily reversed with equimolar doses of scopolamine (SCOP). The effects of 0.02 M ACh were also rapidly reversed by equal volumes of 0.001 M CLON, SCOP and CLON reduced basal firing rates without blocking responses to sensory stimuli. Infusion of the cholinergic agonist carbamyl-beta-choline (carbachol) produced robust, reliable activation of LC neurons at doses of 25-1,000 ng per 100 nl injection. The electrophysiological effects of 3 adrenocorticotropin hormone (ACTH) fragments [1-24], [4-10], and [1-10] were also evaluated. ACTH[1-10] and ACTH[4-10] decreased LC activity for up to 2 hr. ACTH[1-24] exhibited more complex effects, with an increase in discharge rate being accompanied by a decrease in action potential amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

Corticotropin-releasing hormone increases tonic but not sensory-evoked activity of noradrenergic locus coeruleus neurons in unanesthetized rats.

These studies were designed to further test the hypothesis that corticotropin-releasing hormone (CRH) is released from axons innervating the noradrenergic neurons of the locus coeruleus (LC) and serves to activate these neurons during stress responses. Specifically, the effects of exogenous CRH on the electrophysiological activity of LC neurons in unanesthetized rats were characterized. Intracerebroventricular (I.C.V.) injection of CRH (0.3-3.0 micrograms) caused a dose-dependent increase in LC spontaneous discharge rates that became statistically significant 6-9 min after injection and was still evident 30-40 min later. A 1.0 and 3.0 micrograms amount of CRH caused peak increases of 86 +/- 32% and 184 +/- 29% (SEM), respectively. In contrast, neither the lowest dose of CRH (0.3 microgram) nor a high dose of Ala 14CRH (3.0 micrograms), an inactive analog of CRH, altered LC spontaneous activity. The effects of CRH administration on sensory-evoked activity of LC neurons were also determined. As previously reported (Foote et al., 1980; Aston-Jones and Bloom, 1981b), the repeated presentation of auditory tone stimuli resulted in a brief enhancement of LC discharge, which was usually followed by a period of relatively decreased activity. Administration of 1.0 or 3.0 micrograms CRH enhanced basal discharge during sensory testing, but discharge rates during the excitatory component of the sensory response were not altered. Quantitative analyses revealed that these doses of CRH produced a statistically significant decrease in the ratio of sensory-evoked to basal discharge rates. Additional analyses of the temporal distribution of discharge activity for individual recording sites during sensory testing demonstrated that 1.0 and 3.0 micrograms CRH altered relative response magnitudes to a statistically significant extent in 7 of 10 and 5 of 7 cases, respectively, while 0.3 microgram CRH and 3.0 micrograms Ala 14CRH were without effect. The present results are consistent with previous studies of CRH effects on LC activity in anesthetized rats (Valentino et al., 1983; Valentino and Foote, 1987). However, in unanesthetized animals, CRH is more potent in increasing tonic activity and does not decrease the absolute magnitude of sensory-evoked activity. The present results support the hypothesis that CRH released from fibers innervating the LC may affect the tonic activity of these cells and the relationship between tonic discharge and phasic, sensory-evoked activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1988

Corticotropin-releasing factor in olivocerebellar climbing-fiber system of monkey (Saimiri sciureus and Macaca fascicularis): parasagittal and regional organization visualized by immunohistochemistry.

An antiserum directed against the human form of corticotropin-releasing factor (CRF) was utilized for immunohistochemical visualization of the distribution of this peptide in the inferior olivary nucleus and cerebellum of 2 monkey species (Saimiri sciureus, Macaca fascicularis). Colchicine pretreatment was not used. In both species, immunoreactivity was evident in the vast majority of neurons in the inferior olivary nucleus, with perikarya in the medial accessory olive exhibiting especially intense staining. In cerebellum, no labeled perikarya were present, but immunoreactive axons exhibiting the morphological characteristics of climbing fibers and their collaterals were observed in cortical and nuclear structures. In the cortex, most labeled axons were confined to the molecular and Purkinje cell layers. In the sagittal plane, individual axonal arbors originated from thick, isolated axons at the base of the molecular layer and repeatedly ramified as they extended toward the cortical surface. In coronal sections, only thin, paired profiles were present. Labeled processes also formed efflorescences in the granular layer of cortex and were evident as highly arborized axons in cerebellar nuclei. In each of these instances, the labeled elements resembled climbing fibers or their collaterals as visualized by other methods. Other labeled processes in the granular layer exhibited the morphological characteristics of mossy fiber axons. Immunoreactive, climbing-fiber-like axons were present in the molecular layer throughout the major regions of cerebellar cortex. However, the most intensely labeled of these axons were strikingly clustered within particular regions and parasagittal domains. In the vermis and intermediate zone, intensely labeled axons were present only within parasagittal zones similar in location to those defined by climbing fiber innervation from the medial accessory olive. Intensely labeled axons were also densely but uniformly distributed within the uvula, the medial region of the dorsal paraflocculus, and the dorsal region of the pyramis, areas that receive their climbing fiber input primarily from the medial accessory olive. Labeled fibers were much less dense and were not clustered in the lateral hemispheres. The present observation of CRF-like immunoreactivity in the monkey olivocerebellar pathway is compatible with the previous observation of CRF mRNA within olivary neurons of rat, baboon, and human (Young et al., 1986) and with recent immunohistochemical findings in rat (Sakanaka et al., 1987; Palkovits et al., 1987), cat (Cummings et al., 1988; Kitahama et al., 1988), sheep (Cummings et al., 1988), and human (Powers et al., 1987).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Distribution of choline acetyltransferase-, serotonin-, dopamine-beta-hydroxylase-, tyrosine hydroxylase-immunoreactive fibers in monkey primary auditory cortex.

Immunohistochemical methods were used to visualize choline acetyltransferase (ChAT)-, serotonin-, dopamine-beta-hydroxylase (DBH)-, and tyrosine hydroxylase (TH)-containing fibers in the primary auditory cortex of the cynomolgus monkey (Macaca fascicularis). Each antiserum revealed a subpopulation of axons with a distinct density and laminar distribution. ChAT-immunoreactive fibers were very dense in superficial layers, particularly in layers I, deep III, and IV, and very sparse in layers V and VI. No immunoreactive cell bodies were evident. Serotonin-immunoreactive fibers were very dense in all cortical layers but exhibited some subtle laminar differences in fiber size and orientation. The densities of DBH- and TH-immunoreactive fibers were substantially lower than the densities of both ChAT- and serotonin-immunoreactive fibers, particularly in layer IV. However, there were substantial differences between the distribution of TH-immunoreactive fibers and that of DBH-immunoreactive fibers. For example, the density of TH-immunoreactive fibers was substantially greater than that of DBH-immunoreactive fibers in layer I. In addition, TH-immunoreactive fibers differed from the other three systems in that TH-immunoreactive fibers exhibited a rostral to caudal gradient of decreasing density. This is the first characterization of the innervation of a specific cortical region by all four of these systems and the first detailed description of the cholinergic innervation of a primate neocortical region utilizing a specific anti-ChAT antiserum. These striking differences in density and laminar distribution suggest that the subcortical extrathalamic systems furnishing these axons differ significantly in their modulation of cortical auditory processing. These data extend observations of previous studies which revealed that the expansion and specialization of the primate neocortex is accompanied by a pronounced regional and laminar differentiation in the intracortical distribution of these highly divergent, extrathalamic afferents.

Adrenergic Fibers↗