Neurons in the posterior insular cortex are responsive to gustatory stimulation of the pharyngolarynx, baroreceptor and chemoreceptor stimulation, and tail pinch in rats

Extracellular unit responses to gustatory stimulation of the pharyngolaryngeal region, baroreceptor and chemoreceptor stimulation, and tail pinch were recorded from the insular cortex of anesthetized and paralyzed rats. Of the 32 neurons identified, 28 responded to at least one of the nine stimuli used in the present study. Of the 32 neurons, 11 showed an excitatory response to tail pinch, 13 showed an inhibitory response, and the remaining eight had no response. Of the 32 neurons, eight responded to baroreceptor stimulation by an intravenous (i.v.) injection of methoxamine hydrochloride (Mex), four were excitatory and four were inhibitory. Thirteen neurons were excited and six neurons were inhibited by an arterial chemoreceptor stimulation by an i.v. injection of sodium cyanide (NaCN). Twenty-two neurons were responsive to at least one of the gustatory stimuli (deionized water, 1.0 M NaCl, 30 mM HCl, 30 mM quinine HCl, and 1.0 M sucrose); five to 11 excitatory neurons and three to seven inhibitory neurons for each stimulus. A large number of the neurons (25/32) received converging inputs from more than one stimulus among the nine stimuli used in the present study. Most neurons (23/32) received converging inputs from different modalities (gustatory, visceral, and tail pinch). The neurons responded were located in the insular cortex between 2.0 mm anterior and 0.2 mm posterior to the anterior edge of the joining of the anterior commissure (AC); the mean location was 1.2 mm (n=28) anterior to the AC. This indicates that most of the neurons identified in the present study seem to be located in the region posterior to the taste area and anterior to the visceral area in the insular cortex. These results indicate that the insular cortex neurons distributing between the taste area and the visceral area receive convergent inputs from gustatory, baroreceptor, chemoreceptor, and nociceptive organs.     

Cortical and thalamic afferent connections of the insular and adjacent cortex of the rat

Thalamic and cortical afferents to the insular and perirhinal cortex of the rat were investigated. Unilateral injections of horseradish peroxidase (HRP) were made iontophoretically along the rhinal sulcus. HRP injections covered or invaded areas along the rhinal fissure from about the level of the middle cerebral artery to the posterior end of the fissure. The most anterior injection labeled a few cells in the mediodorsal nucleus. More posterior injections labeled neurons in the basal portion of the nucleus ventralis medialis, thus suggesting that this cortical region constitutes the rat's gustatory (insular) cortex. We consider the cortex situated posterior to the gustatory cortex in and above the rhinal sulcus as the core region of the rat's (associative) insular cortex, as this cortex receives afferents from the regions of and between the nuclei suprageniculatus and geniculatus medialis, pars magnocellularis. It includes parts of the cortex termed perirhinal in other studies. The cortex dorsal and posterior to the insular cortex we consider auditory cortex, as it receives afferents from the principal part of the medial geniculate nucleus, and the cortex ventral to the insular cortex (below the fundus of the rhinal sulcus) we consider to constitute the prepiriform cortex, which is athalamic. The posterior part of the perirhinal cortex (area 35) receives afferents from nonspecific thalamic nuclei (midline nuclei). Cortical afferents to the injection loci arise from a number of regions, above all from regions of the medial and sulcal prefrontal cortex. Those injections confined to the projection cortex of the suprageniculate-magnocellular medial geniculate nuclear complex also led to labeling in contralateral prefrontal regions, particularly in area 25 (infralimbic region). A comparison of our results with those on the insular cortex of cats and monkeys suggests that on the basis of thalamocortical connections, topographical relations, and involvements of neurons in information processing and overt behavior, the insular cortex has to be regarded as a heterogeneous region which may be separated into prefrontal insular, gustatory (somatosensory) insular, and associative insular portions.     

Human forebrain activation by visceral stimuli.

Visceral function is essential for survival. Discreet regions of the human brain controlling visceral function have been postulated from animal studies (Cechetto and Saper [1987] J. Comp. Neurol. 262:27-45) and suspected from lethal cardiac arrythmias (Cechetto [1994] Integr. Physiol. Behv. Sci. 29:362-373). However, these visceral sites remain uncharted in the normal human brain. We used 4-Tesla functional magnetic resonance imaging (fMRI) to identify changes in activity in discrete regions of the human brain previously identified in animal studies to be involved in visceral control. Five male subjects underwent heart rate (HR) and/or blood pressure (BP) altering tests: maximal inspiration (MX), Valsalva's maneuver (VM), and isometric handgrip (HG). Increased neuronal activity was observed during MX, VM, and HG, localized in the insular cortex, in the posterior regions of the thalamus, and in the medial prefrontal cortex. To differentiate special visceral (taste) regions from general visceral (HR, BP) regions in these areas, response to gustatory stimulation was also examined; subjects were administered saline (SAL) and sucrose (SUC) solutions as gustatory stimuli. Gustatory stimulation increased activity in the ventral insular cortex at a more inferior level than the cardiopulmonary stimuli. The observed neural activation is the first demonstration of human brain activity in response to visceral stimulation as measured by fMRI.     

Convergence of afferent inputs from the chorda tympani, lingual-tonsillar and pharyngeal branches of the glossopharyngeal nerve, and superior laryngeal nerve on the neurons in the insular cortex in rats

The responses of single neurons in the insular cortex to electrical stimulation of the chorda tympani (CT), lingual-tonsillar branch of the glossopharyngeal (LT-IXth) nerve, pharyngeal branch of the glossopharyngeal (PH-IXth) nerve, and superior laryngeal (SL) nerve were recorded in anaesthetized and paralyzed rats. Ninety-four neurons responding to stimulation of at least one of the four nerves were identified from the insular cortex. Most of the neurons were located in the posterior portion of the insular cortex; the mean location was 0.8 mm anterior to the anterior edge of the joining of the anterior commissure (AC) and was 1.4 mm dorsal to the rhinal fissure (RF). Of the 94 neurons, 84 (89%) received convergent inputs from two or more nerves, and the remaining 10 (11%) received inputs from one nerve. The neurons responding to the CT stimulation were distributed more anteriorly than those responding to other three nerves in the anterior-posterior dimension. Our results indicate that the neurons recorded mainly from the posterior portion of the insular cortex receive convergent inputs from the oropharyngolaryngeal regions.     

Electroacupuncture modulates the activity of the hippocampus-nucleus tractus solitarius-vagus nerve pathway to reduce myocardial ischemic injury

The hippocampus is involved in the regulation of the autonomic nervous system,together with the hypothalamus and brainstem nuclei,such as the paraventricular nucleus and nucleus tractus solitarius.The vagus nerve-nucleus tractus solitarius pathway has an important role in cardiovascular reflex regulation.Myocardial ischemia has been shown to cause changes in the autonomic nervous system,affecting the dynamic equilibrium of the sympathetic and vagal nerves.However,it remains poorly understood how the hippocampus communicates with brainstem nuclei to regulate the autonomic nervous system and alleviate myocardial ischemic tissue damage.A rat model of acute myocardial ischemia(AMI) was made by ligating the left anterior descending branch of the coronary artery.Three days before ischemia,the hippocampal CA1 region was damaged.Then,3 days after ischemia,electroacupuncture(EA) at Shenmen(HT7)-Tongli(HT5) was performed(continuous wave,1 m A,2 Hz,duration of 30 minutes).Cluster analysis of firing patterns showed that one type of neuron was found in rats in the sham and AMI groups.Three types of neurons were observed in the AMI + EA group.Six types of neurons were found in the AMI + EA + Lesion group.Correlation analysis showed that the frequency of vagus nerve discharge in each group was negatively correlated with heart rate(HR)(P 0.05,r =-0.424),and positively correlated with mean arterial pressure(MAP)(P 0.05,r = 0.40987) and the rate-pressure product(RPP)(P 0.05,r = 0.4252).The total frequency of the nucleus tractus solitarius discharge in each group was positively correlated with vagus nerve discharge(P 0.01,r = 0.7021),but not with hemodynamic index(HR: P 0.05,r =-0.03263; MAP: P 0.05,r =-0.08993; RPP: P 0.05,r =-0.03263).Some neurons(Neuron C) were negatively correlated with vagus nerve discharge,HR,MAP and RPP in the AMI + EA group(vagus nerve discharge: P 0.05,r =-0.87749; HR: P 0.01,r =-0.91902; MAP: P 0.05,r =-0.85691; RPP: P 0.01,r =-0.91902).Some neurons(Neurons C,D and E) were positively correlated with vagus nerve discharge,HR,MAP and RPP in the AMI + EA + Lesion group(vagus nerve discharge: P 0.01,r = 0.8905,P 0.01,r = 0.9725,P 0.01,r = 0.9054; HR: P 0.01,r = 0.9347,P 0.01,r = 0.9089,P 0.05,r = 0.8247; MAP: P 0.05,r = 0.8474,P 0.01,r = 0.9691,P 0.01,r = 0.9027; RPP: P 0.05,r = 0.8637,P 0.01,r = 0.9407,P 0.01,r = 0.9027).These findings show that the hippocampus-nucleus tractus solitarius-vagus nerve pathway is involved in the cardioprotective effect of EA at the heart meridian.Some interneurons in the nucleus tractus solitarius may play a particularly important role in the cardiomodulatory process.     

Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: Implications for functional connectivity at rest

Recent studies have demonstrated large amplitude spontaneous fluctuations in functional-MRI (fMRI) signals in humans in the resting state. Importantly, these spontaneous fluctuations in blood-oxygenation-level-dependent (BOLD) signal are often synchronized over distant parts of the brain, a phenomenon termed functional-connectivity. Functional-connectivity is widely assumed to reflect interregional coherence of fluctuations in activity of the underlying neuronal networks. Despite the large body of human imaging literature on spontaneous activity and functional-connectivity in the resting state, the link to underlying neural activity remains tenuous. Through simultaneous fMRI and intracortical neurophysiological recording, we demonstrate correlation between slow fluctuations in BOLD signals and concurrent fluctuations in the underlying locally measured neuronal activity. This correlation varied with time-lag of BOLD relative to neuronal activity, resembling a traditional hemodynamic response function with peaks at approximately 6 s lag of BOLD signal. The correlations were reliably detected when the neuronal signal consisted of either the spiking rate of a small group of neurons, or relative power changes in the multi-unit activity band, and particularly in the local field potential gamma band. Analysis of correlation between the voxel-by-voxel fMRI time-series and the neuronal activity measured within one cortical site showed patterns of correlation that slowly traversed cortex. BOLD fluctuations in widespread areas in visual cortex of both hemispheres were significantly correlated with neuronal activity from a single recording site in V1. To the extent that our V1 findings can be generalized to other cortical areas, fMRI-based functional-connectivity between remote regions in the resting state can be linked to synchronization of slow fluctuations in the underlying neuronal signals.     

A role of insular cortex in cardiovascular function

We sought to determine whether the insular cortex contributes to the regulation of arterial blood pressure (AP). Responses to electrical and chemical stimulation of the cortex were studied in the anesthetized, paralyzed, and artificially ventilated Sprague-Dawley rat. The insular cortex was initially defined, anatomically, by the distributions of retrogradely labeled perikarya following injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the nucleus tractus solitarii (NTS). Injections of WGA-HRP into the insular cortex anterogradely labeled terminals in cardiopulmonary and other divisions of the NTS and confirmed projections revealed by retrograde tracing experiments. Electrical stimulation of the insular cortex elicited elevations of AP (less than or equal to 50 mm Hg) and cardioacceleration (less than or equal to 40 bpm). The locations of the most active pressor sites corresponded closely to the locations of retrogradely labeled cells in layer V of granular and posterior agranular areas of the insular cortex (areas 14 and 13) and the extreme capsule. Maximal pressor responses were obtained at a stimulus intensity of three to five times threshold current of 20-30 microA. Responses elicited mostly with higher-threshold currents were also mapped in areas 2a and 5lb and the claustrum and within the corpus callosum. Unilateral injections into the insular pressor area of the excitatory amino acid monosodium glutamate (L-Glu; 0.05 nmol to 10 nmol) or the rigid structural analogue of L-Glu, kainic acid (KA) (0.4 nmol) (which specifically excite perikarya), caused topographically specific elevations in AP and tachycardia. During the course of the anatomical transport studies, new findings were obtained on the organization and characteristics of the cortical innervation of the NTS and the nucleus reticularis parvocellularis. Topographic relationships between the cortex and the NTS were organized in a more complex manner than previously thought. Cells projecting to caudal cardiopulmonary segments of the NTS were fewer and generally located ventrally and caudally and in a more restricted area than cells projecting rostrally or to the parvicellular reticular formation. Anterograde transport data revealed new presumptive terminal fields in dorsolateral, ventral, periventricular, and commissural regions of the NTS, including an area overlapping the terminal field of the aortic baroreceptor nerve. We conclude that neurons within an area of the insular cortex projecting to multiple brainstem autonomic nuclei, including a region of the NTS innervated by baroreceptor afferents, increase arterial blood pressure and heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)     

Estrogen attenuates neuronal excitability in the insular cortex following middle cerebral artery occlusion

The current investigation examined the role of estrogen in the insular cortex (IC) under both normal and ischemic conditions. Experiments were done in anaesthetized male Sprague-Dawley rats. The effect of systemic 17beta-estradiol (estrogen) administration on levels of amino acids and of endogenous estrogen obtained by microdialysis and its effect on neuronal activity of cells located in the insular cortex were measured in the absence of, and following permanent occlusion of, the right middle cerebral artery (MCA). In normal rats, intravenous (i.v.) injection of estrogen resulted in a significant increase (greater than 25 spikes/bin) in the spontaneous activity of neurons located within the insular cortex, while there was a significant decrease in gamma-aminobutyric acid (GABA) levels measured in IC dialysate. Middle cerebral artery occlusion (MCAO) resulted in a biphasic response consisting of a transient increase in the extracellular concentration of glutamate, aspartate, and GABA, followed by sustained elevations in glutamate and aspartate, but reduced GABA levels 4 h post-MCAO. MCAO also resulted in a significant increase in neuronal activity in the IC (from 28 +/- 9 to 120 +/- 88 spikes/bin). This MCAO-induced excitation was completely blocked following the prior intravenous administration of estrogen. Systemic estrogen administration also resulted in a delay in the progression and decrease in the final infarct volume by approximately 56%. Taken together, these results suggest that under normal conditions, estrogen excites neurons in the insular cortex by decreasing GABA release (disinhibition) and it plays a role in attenuating the MCAO-induced excitability and death of these neurons.     

Reciprocal functional connections of the olfactory bulbs and other olfactory related areas with the prefrontal cortex

Reciprocal putative connections of the prefrontal cortex (PFC) (agranular insular, ventral and lateral orbital region) with the ipsi and contralateral main olfactory bulb (IOB; COB), the mediodorsal thalamic nucleus (MD), the basolateral amygdaloid nucleus (BLA) and the piriform cortex (PC) were investigated with electrophysiological techniques. Evoked field responses and orthodromic unit driving, generated in PFC following electrical stimulation of the above mentioned structures, were abolished following topical application of KCl, except for COB evoked mass potentials. Thus, locally generated activity was elicited in agranular insular cortex following IOB activation, the same region where recently, the taste cortex in the rat was localized. Since gustatory-visceral afferent information reaches insular cortex via 2-3 synaptic relays, autonomic, olfactory and gustatory inputs may interact at this level, and, as suggested previously for the mouse, play a key integrative role in flavor perception. Antidromically invaded neurons, 47% of which were identified by the collision-extinction technique, were also found in PFC areas which overlapped to a considerable extent with those from which orthodromic unit responses were obtained. In particular, closely spaced neurons in ventrolateral orbital (VLO) and lateral orbital (LO) regions were antidromically invaded following IOB and PC shocks; some neurons antidromically discharged by IOB were also transsynaptically activated following PC stimulation. These findings are in agreement with recent neuroanatomical studies which demonstrate axonal projections from PFC neurons to the IOB and COB in the rat and South American armadillo. In addition, stimulation of PFC regions dorsal to the rhinal fissure mostly inhibited spontaneous unit discharges recorded at the mitral cell layer of the IOB, suggesting that this effect may be partially mediated by excitatory inputs of prefrontal axons onto granule cells. The conduction properties, antidromic thresholds and activity-dependent variations in conduction velocity (CV) of bulbopetal neurons in prefrontal cortex were found to be similar to those exhibited by cells projecting to the IOB from olfactory peduncle regions, but not to those present in bulbopetal neurons of the horizontal limb of diagonal band, indicating that the OB may be subjected to centrifugal control by at least two cell groups differing in both histochemical and electrophysiological properties.     

Autonomic responses and efferent pathways from the insular cortex in the rat

The anatomical distribution of autonomic, particularly cardiovascular, responses originating in the insular cortex was examined by using systematic electrical microstimulation. The localization of these responses to cell bodies in the insular cortex was demonstrated by using microinjection of the excitatory amino acid, D,L-homocysteic acid. The efferents from the cardiovascular responsive sites were traced by iontophoretic injection of the anterograde axonal tracer Phaseoleus vulgaris leucoagglutinin (PHA-L). Two distinct patterns of cardiovascular response were elicited from the insular cortex: an increase in arterial pressure accompanied by tachycardia or a decrease in arterial pressure with bradycardia. The pressor responses were obtained by stimulation of the rostral half of the posterior insular cortex while depressor sites were located in the caudal part of the posterior insular area. Both types of site were primarily located in the dysgranular and agranular insular cortex. Gastric motility changes originated from a separate but adjacent region immediately rostral to the cardiovascular responsive sites in the anterior insular cortex. Tracing of efferents with PHA-L indicated a number of differences in connectivity between the pressor and depressor sites. Pressor sites had substantially more intense connections with other limbic regions including the infralimbic cortex, the amygdala, the bed nucleus of the stria terminalis and the medial dorsal and intralaminar nuclei of the thalamus. Alternatively, the depressor region of the insular cortex more heavily innervated sensory areas of the brain including layer I of the primary somatosensory cortex, a peripheral region of the sensory relay nuclei of the thalamus and the caudal spinal trigeminal nucleus. In addition, there were topographical differences in the projection to the lateral hypothalamic area, the primary site of autonomic outflow for these responses from the insular cortex. These differences in connectivity may provide the anatomic substrate for the specific cardiovascular responses and behaviors integrated in the insular cortex.     

Transition from spindles to generalized spike and wave discharges in the cat: Simultaneous single-cell recordings in cortex and thalamus

The relationships between the activity of the cortex and that of a “specific” (n. lateralis posterior, LP) and an intralaminar thalamic nucleus (n. centralis medialis, NCM) were studied in the cat during the transition from spontaneous spindles to generalized spike and wave (SW) discharge following i.m. penicillin injection. The EEG and extracellular single-unit activity were recorded in cortex and thalamus during the spindle stage and at different intervals after penicillin until well developed SW discharges were present. Computer-generated EEG averages and histograms of single-unit activity were triggered by either peaks of cortical or thalamic EEG transients or by cortical or thalamic action potentials. In agreement with previous observations, cortical neurons increasingly fired during the spindle wave as it was transformed into the “spike” of the SW complex, while a period of neuronal silence gradually developed as the “wave” of the SW complex emerged. Similar changes developed in the thalamus, particularly in LP, either concurrently with or more often after the onset of the changes in the cortex. Most neurons in NCM, continued to fire randomly even after well developed SWs and rhythmic neuronal discharges had developed in cortex and LP. Only $\text{4}\text{11}$ NCM neurons did ultimately exhibit a rhythmic firing pattern similar to that seen in the cortex and LP. The correlation between cortical and thalamic unit activity was low during spindles, but gradually increased during the development of SW discharges. These data confirm that the cortex is the leading element in the transition from spindles to SWs. Increasingly, in the course of this transition, cortical and thalamic neuronal firing becomes more intimately phase-locked. This mutual interrelationship appears to be more pronounced between cortex and “specific” than intralaminar thalamic nuclei.     

Neuronal activity in the basal ganglia and thalamus in patients with dystonia.

OBJECTIVE: To explore the role of abnormal neuronal activity in the basal ganglia and thalamus in the generation of dystonia. METHODS: Microelectrode recording was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucleus (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) during surgery. Electromyogram (EMG) was simultaneously recorded in selected muscle groups. Single unit analysis and cross-correlations were carried out. RESULTS: Three hundred and sixty-seven neurons were obtained from 29 trajectories (GPi: 13; Vop/Vim: 12; STN: 4), 87% exhibited altered neuronal activity including grouped discharges in GPi (n=79) and STN (n=37), long-lasting neuronal activity (n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EMG at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0.64 (n=18) and STN: r2=0.86 (n=17)). CONCLUSIONS: Consistent with previous findings of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the present data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the production of dystonic movement. Dystonia-related neuronal activity observed in motor thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the development of either generalized or focal dystonia. SIGNIFICANCE: These data support a central role of the basal ganglia in producing dystonic movements.     

Calcitonin gene-related peptide immunoreactivity in the visceral sensory cortex, thalamus, and related pathways in the rat

It has been proposed that calcitonin gene-related peptide (CGRP) may serve as a major neuromodulator in visceral sensory pathways, but its exact role in the visceral sensory thalamus and cortex has not been determined. We therefore examined the distribution of CGRP-like immunoreactive (CGRPir) innervation of the insular cortex and the parvicellular division of the ventroposterior nucleus of the thalamus (VPpc) in the rat by using immunohistochemistry for CGRP combined with retrograde transport of the fluorescent dye fluoro-gold. Modest numbers of CGRPir fibers were distributed in the dysgranular and agranular insular cortex, but few were observed in the granular insular cortex. The density of CGRPir innervation increased caudally along the rhinal fissue and was considerably greater in the perirhinal cortex. When fluoro-gold was injected into the insular cortex numerous retrogradely labeled neurons were seen in the VPpc, but few of these were CGRPir. Retrogradely labeled CGRPir neurons were, however, seen in the ventral lateral and medial parabrachial (PB) subnuclei. Injection of fluoro-gold into the perirhinal cortex (which is just caudal to the insular cortex along the rhinal fissure) resulted in many retrogradely labeled CGRPir neurons in the posterior thalamic region, including the subparafascicular, the lateral subparafascicular, and the posterior intralaminar nuclei. The VPpc was heavily innervated by CGRPir fibers but contained few CGRPir cell bodies. Injection of fluoro-gold into the VPpc resulted in many retrogradely labeled CGRPir neurons in the external medial PB subnucleus bilaterally, but with a contralateral predominance. Smaller numbers of retrogradely labeled CGRPir neurons were also observed in the ventrolateral PB subnucleus, bilaterally with an ipsilateral predominance. These results suggest that CGRP may be a neuromodulator in the ascending visceral sensory pathways from the PB to the VPpc and the insular cortex, but not between the latter two structures.     

Interdependence of rostral and caudal ventrolateral medullary areas in the control of blood pressure

Pharmacologic experiments were carried out to test the degree of interdependence of rostral vasopressor and caudal vasodepressor neuron pools in the ventrolateral medulla (VLPA and VLDA, respectively). In two groups of urethane-anesthetized rats, the γ-aminobutyric acid (GABA) agonist muscimol (10 ng/site) was bilaterally microinjected into both the VLPA and VLDA to inhibit neuronal activity at these sites. In one group of experiments, muscimol was microinjected first into the VLPA and then into the VLDA. Following muscimol microinjection in the VLPA the mean arterial pressure (MAP) and heart rate (HR) decreased to 40 ± 6 mm Hg and 310 ± 21 beats/min (bpm) from a control level of 90 ± 3 mm Hg and 403 ± 23 bpm. Subsequent microinjection of muscimol in the VLDA had no significant effect on BP or HR. This lack of response was not due to severe fall in BP caused by microinjection of muscimol into the VLPA. In the second group of experiments muscimol was first injected into the VLDA followed by muscimol microinjection into the VLPA. In the VLDA muscimol significantly increased MAP and HR to 139 ± 4 mm Hg and 427 ± 4 bpm from a control level of 87 ± 2 mm Hg and 356 ± 23 bpm. The aortic depressor nerve response (−37 ± 1 mm Hg and −47 ± 4 bpm) was converted to an aortic ‘pressor’ response (+20 ± 1 mm Hg and −13 ± 6 bpm). Subsequent microinjection of muscimol into the VLPA caused MAP and HR to fall to 43 ± 5 mm Hg and 338 ± 17 bpm. The aortic ‘pressor’ response was also abolished (2 ± 2 mm Hg). These results indicate that neuronal activity in the rostral VLPA is an important determinant for changes in BP and its reflex regulation mediated by the VLDA. However, BP changes mediated by the rostral VLPA are independent of the level of neuronal activity in the VLDA. Sites of VLPA and VLDA interaction are discussed.     

Direct projections from the medulla oblongata to selective cortical areas in the rat

Injections of horseradish peroxidase into different cortical areas reveal that neurons located in the rostroventral medulla oblongata innervate restricted cortical areas: the anterior and posterior cingulate cortex and the insular cortex. Other cortical areas do not receive medullary projections. Neurons projecting to both the anterior and the posterior cingulate cortex lie scattered throughout a wide territory of the ventrorostral medulla, whereas neurons projecting to the insular cortex are restricted to more medial regions.     

Insular cortex lesions alter baroreceptor sensitivity in the urethane-anesthetized rat

Cardiovascular representation has been demonstrated within the insular cortex and lateralization has been previously inferred. In this study, baroreceptor gain was investigated in response to the systemic injection of the pressor agent phenylephrine (PE) and the depressor agent sodium nitroprusside (SNP) in 57 urethane-anesthetized, male Sprague–Dawley rats before and after single lesion placement. Lesions mainly confined to the anterior insula (left or right) or the adjacent cortex were without significant effect on baroreceptor gain. Left posterior insular lesions, however, significantly increased baroreceptor gain (p<0.0001) whereas right posterior insular lesions had no effect on baroreceptor gain although heart rate and blood pressure were both significantly increased after lesion placement (p<0.05). These data suggest that: (1) the posterior insula (and not surrounding cortex or anterior insula) is primarily involved in cardiovascular control; (2) the left insular cortex may be chiefly concerned with parasympathetic cardiac regulation. Conversely, the right posterior insular cortex may regulate both cardiac and vasomotor sympathetic tone, as has been suggested in other species.     

Neural correlates to action and rewards in the rat posterior cingulate cortex

To investigate the involvement of the posterior cingulate cortex in reward-based learned actions, we examined its neuronal activities in rats that were trained in a delayed stimulus-response association task. Of the 344 neurons recorded, 178 responded during licking a spout to acquire rewards (a sucrose solution or intracranial self-stimulation). Of these 178 reward-responsive neurons, 80 responded exclusively during licking to acquire sucrose solution, and 20 during licking to acquire intracranial self-stimulation, with 37 of these 100 neurons displaying differential correlation to individual licking on the basis of the reward type. The present results and comparison with previous studies on the anterior cingulate cortex suggest that the posterior cingulate cortex is involved in the monitoring or storage of action-reward outcome association.     

Free Communications (Section D)

In TCD studies, the pulsatility index (PI), which is based on flow waveform analysis, are widely used for assessment of cerebral vascular resistance (CVR). However, PI is not very accurate, because it has many sources of variability and error. We propose a ratio between mean arterial pressure (MAP) and mean velocity (Vm) for an index of CVR. If we assume that the lumen of basal cerebral vessels is constant than MAPNm should be directly proportional to CVR. The aim of our study was to evaluate validity of MAPNm. For this purpose different vasodilatatory stimuli, which affected cerebral resistance and conductive vessels, were used. Hyperventilation (HV) and rebreathing (RE) change blood pCO2, which has predominantly an influence on resistance vessels. Clonidine, alfa-adrenegic blocker, produce vasodilation on perifery. L-arginine (L-arg), precursor of nitro oxide, supposed to be able to induce vasodilatation of cerebral vessels. Nitroglicerinc (NTG) acts primarily on conductive vessels. Ten heathy subjects, both gender, aged from 21 to 57 years (mean 33.4+?11.9 years) participated in our study. HV and RE were performed using capnograph (Oxicap, Ohmeda) We registered end-tidel (ET) CO2. Clonidin was administrated intramusculary at dose? L-arg was infused at rate 5mg/kg/min for 30 minutes. NTG was applied sublingualy at dose 0.6 mg. The response of cerebral circulation was continously monitored by Multi-dop X (OWL, Germany), usmg bitemporal probes for recording of Vm in middle cerebral artenes. Simultaneously the MAP and heart rate (HR) were sampled by pletysmographic device (Finapress. Ohmeda, USA).During RE MAP increased (p=.035), HR did not change, PI (p=.0006) and MAP/Vm (p=.0002) decreased. Dunng HV MAP decreased (p=014), HR increased (p=.048), PI (p=.0001) and MAPNm (p<0001) increased. We found good correlation between changes of PI and MAPNm (r=73, p<01) as well as between changes of MAP/Vm and ET CO2 (r=78, p<01) and moderate correlation between changes of PI and ET CO2 (r=53, p=016) After Clonidine administration MAP decreased (p<0001). HR did not change significantly,PI (p=.04) as well as MAP/Vm (p=.017) decreased. There was no correlation between PI and MAV/Vm. After L=arg infusion MAP and HR did not change, while PI (p<.001) and MAP/Vm (p<.001) decreased. No correlation between PI and MAP/Vm was found. After NTG MAP decreased (p=0.019), HR did not change as well as PI, while MAP/Vm (p=0084) mcrcased There was no correlation between PI and MAP/Vm     

The rostral ventrolateral medulla mediates suppression of the circulatory system by the ventromedial nucleus of the hypothalamus

We recently reported that a train of episodic neural discharges within the ventromedial nucleus of the hypothalamus (VMH) associated with suppression of the circulatory system had been determined by monitoring multiple unit activity (MUA). Abrupt increases in neural activity (MUA volleys; 1 to 4 min in duration) accompanied transient decreases in heart rate (HR) and blood pressure (BP), and showed circadian rhythm, occurring every 15 to 30 min in the light phase but seldom in the dark phase. The present study was aimed to determine if neurons in the vasomotor area of the rostral ventrolateral medulla (RVL) are involved in this VMH-induced cardiovascular suppression. MUAs of the VMH and RVL were monitored simultaneously with HR and BP in urethane-anesthetized rats. In synchrony with each MUA volley in the VMH, spontaneous activity of RVL neurons significantly decreased, as well as HR and BP. These RVL neurons are most likely vasomotor neurons because MUA of the RVL was attenuated by baroreceptor reflex activation, and electrical stimulation of these cells through the MUA recording electrodes produced pressor responses. These data suggest that VMH neurons that show a train of episodic discharges suppress the circulatory system at least in part by inhibiting the excitability of vasomotor neurons in the RVL.     

A blood pressure lowering effect of lesions of the caudal periaqueductal gray: relationship to basal pressure

Basal mean arterial pressure (MAP) measured one week following placement of pontine lesions was markedly lower (-27.85 mm Hg) in cats with bilateral lesions of the caudal periaqueductal gray than in cats with bilateral lesions of the area anteroventral to the locus coeruleus. Regression models of the relationship between basal arterial pressure (MAPbasal) and the change in arterial pressure (MAPchange) after the lesions indicate that lesions of the caudal periaqueductal gray led to a marked decrease in MAP in animals with an elevated basal MAP (MAPchange = MAPbasal x (-1.182) + 139.433; r = -0.902; P less than 0.002). In contrast, lesions of the area anteroventral to the locus coeruleus had no such effect (MAPchange = MAPbasal x (-0.363) + 56.49; r = -0.375; P greater than 0.1). The region of the caudal periaqueductal gray affecting MAP appears anterior to the locus coeruleus and through intrinsic neurons or fibers of passage may play a critical role in control of arterial pressure.