Microinjection Of Glutamate Research Articles

Effects of intertrigeminal region NMDA and non-NMDA receptors on respiratory responses in rats

Respiratory disturbance, including apnea, can be induced by microinjection of glutamate into the intertrigeminal region (ITR) of the lateral pons, a region that is anatomically coupled to both the dorsal and ventral respiratory groups of the medulla. We showed that the ITR plays a functional role in regulating both vagal reflex apnea and spontaneous sleep-related apnea in rats, but the mechanisms have not been determined. This study shows that functional NMDA receptors are expressed in the ITR since the blockade of these receptors by AP5, a specific NMDA receptor antagonist, was fully effective in blocking apnea induced by glutamate injection within this region. Selective blockade of ITR NMDA receptors had no effect on the immediate apnea evoked by an intravenous 5-HT bolus, whereas the nonspecific glutamate receptor antagonist kynurenic acid significantly increased the duration of this vagal reflex apnea. These findings are of interest because pontine NMDA receptors participate in inspiratory off-switch mechanisms and have been implicated in various short- and long-term potentiation and depression phenomena. These data support the involvement of ITR non-NMDA receptors in modulation of reflex apnea per se, whereas NMDA receptors play a role in damping respiratory responses to transient disturbances.

Differential influence of iNOS and nNOS inhibitors on rostral ventrolateral medullary mediated cardiovascular control in conscious rats

We evaluated the cardiovascular effects of nitric oxide (NO) inhibitors microinjected into the rostral ventrolateral medulla (RVLM) of conscious rats. Application of L‐NAME or aminoguanidine (AG) induced an increase in arterial blood pressure (MAP) and an increase in heart rate, whereas 7‐nitroindazole (7‐NI) decreased MAP and HR. Microinjection of glutamate produced an increase in MAP which was followed by either a tachycardia or a bradycardia. Such responses were blocked totally by prior administration of L‐NAME and attenuated (∼ 50%) by 7‐NI. In contrast, glutamate responses were enhanced by following AG. We conclude that in conscious rats, NO has tonic effects in the RVLM and may participate in the modulation of the actions of glutamate through iNOS and nNOS pathways.

The Kölliker‐Fuse nucleus gates the postinspiratory phase of the respiratory cycle to control inspiratory off‐switch and upper airway resistance in rat

Lesion or pharmacological manipulation of the dorsolateral pons can transform the breathing pattern to apneusis (pathological prolonged inspiration). Apneusis reflects a disturbed inspiratory off-switch mechanism (IOS) leading to a delayed phase transition from inspiration to expiration. Under intact conditions the IOS is irreversibly mediated via activation of postinspiratory (PI) neurons within the respiratory network. In parallel, populations of laryngeal premotoneurons manifest the IOS by a brief glottal constriction during the PI phase. We investigated effects of pontine excitation (glutamate injection) or temporary lesion after injection of a GABA-receptor agonist (isoguvacine) on the strength of PI-pool activity determined from respiratory motor outputs or kinesiological measurements of laryngeal resistance in a perfused brainstem preparation. Glutamate microinjections into distinct parts of the pontine Kölliker-Fuse nucleus (KF) evoked a tonic excitation of PI-motor activity or sustained laryngeal constriction accompanied by prolongation of the expiratory phase. Subsequent isoguvacine microinjections at the same loci abolished PI-motor or laryngeal constrictor activity, triggered apneusis and established a variable and decreased breathing frequency. In summary, we revealed that excitation or inhibition of defined areas within the KF activated and blocked PI activity and, consequently, IOS. Therefore, we conclude, first, that descending KF inputs are essential to gate PI activity required for a proper pattern formation and phase control within the respiratory network, at least during absence of pulmonary stretch receptor activity and, secondly, that the KF contains large numbers of laryngeal PI premotor neurons that might have a key role in the regulation of upper airway resistance during reflex control and vocalization.

Interaction between glutamate and GABA systems in the integration of sympathetic outflow by the paraventricular nucleus of the hypothalamus

The paraventricular nucleus (PVN) of the hypothalamus is a central site known to modulate sympathetic outflow. Excitatory and inhibitory neurotransmitters within the PVN dictate final outflow. The goal of the present study was to examine the role of the interaction between the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA in the regulation of sympathetic activity. In alpha-chloralose- and urethane-anesthetized rats, microinjection of glutamate and N-methyl-D-aspartate (NMDA; 50, 100, and 200 pmol) into the PVN produced dose-dependent increases in renal sympathetic nerve activity, blood pressure, and heart rate. These responses were blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5). Microinjection of bicuculline, a GABA(A) receptor antagonist, into the PVN (50, 100, and 200 pmol) also produced significant, dose-dependent increases in renal sympathetic nerve activity, blood pressure, and heart rate; AP-5 also blocked these responses. Using microdialysis and HPLC/electrochemical detection techniques, we observed that bicuculline infusion into the PVN increased glutamate release. Using an in vitro hypothalamic slice preparation, we found that bicuculline increased the frequency of glutamate-mediated excitatory postsynaptic currents in PVN-rostral ventrolateral medullary projecting neurons, supporting a GABA(A)-mediated tonic inhibition of this excitatory input into these neurons. Together, these data indicate that 1) glutamate, via NMDA receptors, excites the presympathetic neurons within the PVN and increases sympathetic outflow and 2) this glutamate excitatory input is tonically inhibited by a GABA(A)-mediated mechanism.

Differential baroreceptor modulation mediated by the ventrolateral medulla

Previous studies have shown that pharmacological stimulation of a region denominated caudal pressor area (CPA), located in the caudal end of the ventrolateral medulla, induces increases in arterial blood pressure (BP). The aim of this study was to compare the responses on renal sympathetic nerve activity (rSNA) and BP responses mediated by stimulation of CPA or rostral ventrolateral medulla (RVLM), in intact or sino-aortic barodenervated rats. Male Wistar rats (300–350 g, n = 15) were anesthetized (urethane 1.2 to 1.4 g/kg, i.v.) and artificially ventilated. The mean arterial pressure (MAP) and rSNA were measured during bilateral glutamate microinjection (10 nmo/100 nl) into the CPA or into the RVLM. Glutamatergic stimulation of the RVLM increased MAP (46 ± 7 mm Hg) and rSNA (82 ± 21%); during CPA stimulation, MAP and rSNA increased 60 ± 7 mm Hg and 93 ± 9%, respectively. However, despite the similarity of responses mediated by both regions, the duration of rSNA and blood pressure responses mediated by the CPA were significantly longer than the duration of the responses mediated by the RVLM. After barodenervation, there was an increase in the time-course and magnitude of sympathetic response only in response to RVLM stimulation but not in response to CPA. The results suggest a differential baroreceptor modulation on rSNA mediated by the ventrolateral medulla neurons. Glutamatergic activation of CPA neurons can cause large increases in the rSNA and BP with a weaker baroreceptor modulation when compared to responses mediated by the RVLM neurons.

Responses mediated by the RVLM on splancnic and renal sympathetic nerve activity in heart failure rats

The aim o the present study was to evaluate the glutamatergic and GABAergic actions in the rostral ventrolateral medulla (RVLM) on splancnic (sSNA) and renal (rSNA) sympathetic nerve activity in heart failure rats (HF). Male Wistar rats developed heart failure by ligating the left anterior descending coronary artery. Sham-operated rats were submitted to the same surgical procedure without coronary ligation. Three weeks after surgery, echocardiography was performed under ketamine-xilazine sedation. Only animals with large infarctions (40 – 65% ischemic zone) were used in the present study. Under urethane (1.4 g/Kg, iv) anesthesia, renal and splancnic SNA were recorded (50-1000 Hz). The rSNA increased in HF in comparison to control group (HF 151± 13 Hz, control 116±10 Hz), p<0,05). In relation to sSNA there was no difference between groups (HF 125± 8 Hz, control 111±6 Hz). Bilateral microinjection of glutamate (10 nmol/100nl) into the RVLM resulted in similar increases of MAP (HF from 98±9 to 138±16 mmHg; control from 103±6 to 141±8 mmHg), sSNA (HF 52±7%; control 44±8%) and rSNA (HF 51±8%, control 46±5%). No difference between groups was observed in response to GABA microinjection into the RVLM, there was a decrease in MAP (HF from 105±9 to 68±2 mmHg; control from 102±6 to 54±3 mmHg), sSNA (HF −49±2%; control −51±5%) and rSNA (HF −70±16%; control −53±9%). Taken altogether, our results suggest a differential increase in the rSNA but not in the sSNA in HF rats. However, the excitatory and inhibitory amino acids in the RVLM evoked the same responses between groups. Financial support FAPESP – CNPq (PRONEX)

Modulation of the Hering-Breuer reflex by raphe pallidus in rabbits

Activation of the pulmonary stretch receptors by lung inflation or vagal stimulation evokes Hering-Breuer (HB) reflex, which is characterized by inspiratory inhibition and expiratory prolongation. In this work, whether the HB reflex could be modulated by the serotonergic raphe pallidus (RP) was studied by comparing the strength of this reflex before and after electrical or chemical stimulation of the RP. Experiments were performed on urethane anesthetized adult rabbits. The HB reflex was simulated with electrical stimulation of the central end of cervical vagus nerve. The RP was stimulated electrically or chemically by microinjection of glutamate. We found that after either electrical stimulation or chemical stimulation of the RP, the inspiratory inhibition and expiratory prolongation of the HB reflex were significantly attenuated. This attenuation showed post-stimulation time dependency or short-term memory, as well as RP stimulation intensity dependency. Results of the present study suggested that the serotonergic RP could exert its respiratory effects by modulating the strength of HB reflex.

Inhibition of nociceptive neurons in the medullary dorsal horn by glutamate microinjection into the amygdala of the rat

Inhibition of nociceptive neurons in the medullary dorsal horn by glutamate microinjection into the amygdala of the rat

Putative role of the NTS in alterations in neural control of the circulation following exercise training in rats

Exercise training (ExTr) has been associated with alterations in neural control of the circulation, including effects on arterial baroreflex function. The nucleus tractus solitarius (NTS) is the primary termination site of cardiovascular afferents and critical in the regulation of baroreflex-mediated changes in heart rate (HR) and sympathetic nervous system outflow. The purpose of the present study was to determine whether ExTr is associated with alterations in neurotransmitter regulation of neurons involved in control of cardiovascular function at the level of the NTS. We hypothesized that ExTr would increase glutamatergic and reduce GABAergic transmission in the NTS and that, collectively, these changes would result in a greater overall sympathoinhibitory drive from the NTS in ExTr animals. To test these hypotheses, male Sprague-Dawley rats were treadmill trained or maintained under sedentary conditions for 8-10 wk. NTS microinjections were performed in Inactin-anesthetized animals instrumented to record mean arterial pressure (MAP), HR, and lumbar sympathetic nerve activity (LSNA). Generalized activation of the NTS with unilateral microinjections of glutamate (1-10 mM, 30 nl) produced dose-dependent decreases in MAP, HR, and LSNA that were unaffected by ExTr. Bilateral inhibition of NTS with the GABAA agonist muscimol (1 mM, 90 nl) produced increases in MAP and LSNA that were blunted by ExTr. In contrast, pressor and sympathoexcitatory responses to bilateral microinjections of the ionotropic glutamate receptor antagonist, kynurenate (40 mM, 90 nl), were similar between groups. Bradycardic responses to bilateral microinjections of the GABAA antagonist bicuculline (0.1 mM, 90 nl) were attenuated by ExTr. These data indicate that alterations in neurotransmission at the level of the NTS contribute importantly to regulation of HR and LSNA in ExTr animals. In addition to alterations at NTS, these experiments suggest indirectly that changes in other cardiovascular nuclei contribute to the observed alterations in neural control of the circulation following ExTr.

Attenuated pressor responses to amino acids in the rostral ventrolateral medulla after swimming training in conscious rats

The cardiovascular effects of microinjection of the amino acids glutamate and glycine within the rostral ventrolateral medulla (RVLM) after swimming training (ST) in unrestrained awake rats were investigated. Unilateral microinjection of l-glutamate (5, 20 and 50 mM, in 100 nl) produced a dose dependent increase in mean arterial pressure (MAP) in control (C) (16 ± 5 mm Hg; 29 ± 6 mm Hg; 43 ± 6 mm Hg) and swim (SW) (1 ± 1 mm Hg; 16 ± 2 mm Hg; 25 ± 3 mm Hg) groups. However, the magnitude of this response was lower in the swim group. Prazosin injection produced hypotension and tachycardia in both groups (C = − 43 ± 3 mm Hg/98 ± 16 bpm; SW = − 61 ± 5 mm Hg/115 ± 32 bpm). In the SW group the hypotension caused by prazosin was greater compared to C group, but the tachycardia was not different between them. After prazosin, glutamate response in RVLM was blocked in both groups as well. When glycine (10 mM or 1 M, in 100 nl) were microinjected into the RVLM of C group we observed two different effects: decrease in MAP with the lower dose and an increase in MAP with the higher dose (10 mM = − 13 ± 2 mm Hg; 1 M = 47 ± 6 mm Hg). However, after ST the hypertensive response to glycine was blunted with no alterations in the hypotensive response (10 mM = − 14 ± 1 mm Hg; 1 M = 18 ± 4 mm Hg). These findings suggest that RVLM is involved in the modulation of the sympathetic outflow to the cardiovascular system during exercise training.

Cholinergic systems in the posterior hypothalamic nucleus are involved in blood pressure decrease-induced excitation of anterior hypothalamic area neurons in rats

Previously, we have demonstrated that decreases in blood pressure induced by intravenous nitroprusside increase the firing rate of angiotensin II-sensitive neurons in the anterior hypothalamic area (AHA) of rats and that this increase of neural firing rate is blocked by the pressure application of losartan onto the same neurons. It has been suggested that acetylcholine in the posterior hypothalamic nucleus (PHN) serves as a neurotransmitter in a pathway which can modulate baroreceptor reflexes. In the present study, we examined whether acetylcholine in the PHN is involved in the nitroprusside-induced increase of the firing of angiotensin II-sensitive neurons in the AHA of rats. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Decreases in blood pressure induced by intravenous nitroprusside (100 ug/kg) increased the firing rate of AHA angiotensin II-sensitive neurons. The nitroprusside-induced increase of firing rate of AHA neurons was inhibited by PHN microinjection of the cholinoceptor antagonist scopolamine and potentiated by PHN microinjection of the cholinesterase inhibitor physostigmine. Microinjections of carbachol and glutamate into the PHN caused increases of firing rate of AHA neurons. The carbachol-induced but not glutamate-induced increase of unit firing was abolished by the pre-microinjection of scopolamine into the same sites of the PHN. These findings suggest that the nitroprusside-induced increase of firing of AHA neurons is mediated via acetylcholine at the level of the PHN.

Involvement of reticular neurons located dorsal to the facial nucleus in activation of the jaw-closing muscle in rats

The location of excitatory premotor neurons for jaw-closing motoneurons was examined by the use of electrical and chemical stimulation and extracellular single-unit recording techniques in the anesthetized rat. Single-pulse electrical stimulation of the supratrigeminal region (SupV) and the reticular formation dorsal to the facial nucleus (RdVII) elicited masseter EMG response at mean (±SD) latencies of 2.22 ± 0.59 ms and 3.10 ± 1.14 ms, respectively. Microinjection (0.1–0.3 μl) of glutamate (50 mM) or kainate (0.5–100 μM) into RdVII increased masseter nerve activity in artificially ventilated and immobilized rats by 30.2 ± 40.5% and 50.7 ± 46.8% compared to baseline values, respectively. Forty reticular neurons were antidromically activated by stimulation of the ipsilateral trigeminal motor nucleus (MoV). Twenty neurons were found in RdVII, and the remaining 20 neurons were located in SupV, or areas adjacent to SupV or RdVII. Eleven neurons in RdVII responded to at least either passive jaw opening or light pressure applied to the teeth or tongue. Nine neurons responded to passive jaw opening. Five of the nine neurons responded to multiple stimulus categories. A monosynaptic excitatory projection from one neuron in RdVII was detected by spike-triggered averaging of the rectified masseter nerve activity. We suggest that reticular neurons in RdVII are involved in increasing masseter muscle activity and that excitatory premotor neurons for masseter motoneurons are likely located in this area. RdVII could be an important candidate for controlling activity of jaw-closing muscles via peripheral inputs.

Cholinergic stimulation in the posterior hypothalamic nucleus activates angiotensin II-sensitive neurons in the anterior hypothalamic area of rats

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats (SHR). Acetylcholine in the posterior hypothalamic nucleus (PHN) has been implicated in hypertension in SHR. It is suggested that there exist neuronal projections from the PHN to the AHA in rats. In this study, we examined whether cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of carbachol, physostigmine and glutamate into the PHN caused an increase in firing rate of AHA angiotensin II-sensitive neurons in anesthetized rats. The carbachol-induced increase of firing rate was inhibited by pressure application of the AT1 receptor antagonist losartan onto AHA angiotensin II-sensitive neurons. The glutamate-induced increase of firing rate was also inhibited by the pressure application of losartan. PHN microinjections of carbachol and glutamate did not affect blood pressure in these anesthetized rats. In conscious rats, PHN microinjection of carbachol produced an increase of blood pressure and the carbachol-induced pressor response was inhibited by bilateral microinjections of losartan into the AHA. These findings indicate that cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. It seems likely that the activation of AHA angiotensin II-sensitive neurons induced by PHN cholinergic stimulation is partly mediated via release of angiotensins at AHA angiotensin II-sensitive neuron levels.

A subsidiary fever center in the medullary raphé?

In fever, as in normal thermoregulation, signals from the preoptic area drive both cutaneous vasoconstriction and thermogenesis by brown adipose tissue (BAT). Both of these responses are mediated by sympathetic nerves whose premotor neurons are located in the medullary raphé. EP3 receptors, key prostaglandin E2 (PGE2) receptors responsible for fever induction, are expressed in this same medullary raphé region. To investigate whether PGE2 in the medullary raphé might contribute to the febrile response, we tested whether direct injections of PGE2 into the medullary raphé could drive sympathetic nerve activity (SNA) to BAT and cutaneous (tail) vessels in anesthetized rats. Microinjections of glutamate (50 mM, 60-180 nl) into the medullary raphé activated both tail and BAT SNA, as did cooling the trunk skin. PGE2 injections (150-500 ng in 300-1,000 nl) into the medullary raphé had no effect on tail SNA, BAT SNA, body temperature, or heart rate. By contrast, 150 ng PGE2 injected into the preoptic area caused large increases in both tail and BAT SNA (+60 +/- 17 spikes/15 s and 1,591 +/- 150% of control, respectively), increased body temperature (+1.8 +/- 0.2 degrees C), blood pressure (+17 +/- 2 mmHg), and heart rate (+124 +/- 19 beats/min). These results suggest that despite expression of EP3 receptors, neurons in the medullary raphé are unable to drive febrile responses of tail and BAT SNA independently of the preoptic area. Rather, they appear merely to transmit signals for heat production and heat conservation originating from the preoptic area.

Involvement of Kv1 Potassium Channels in Spreading Acidification and Depression in the Cerebellar Cortex

Spreading acidification and depression (SAD) is a form of propagated activity in the cerebellar cortex characterized by acidification and a transient depression in excitability. This study investigated the role of Kv1 potassium channels in SAD using neutral red, flavoprotein autofluorescence, and voltage-sensitive dye optical imaging in the mouse cerebellar cortex, in vivo. The probability of evoking SAD was greatly increased by blocking Kv1.1 as well as Kv1.2 potassium channels by their specific blockers dendrotoxin K (DTX-K) and tityustoxin (TsTX), respectively. DTX-K not only greatly lowered the threshold for evoking SAD but also resulted in multiple cycles of spread and spontaneous SAD. The occurrence of spontaneous SAD originating from spontaneous parallel fiber-like beams of activity suggests that blocking Kv1 channels increased parallel fiber excitability. This was confirmed by the generation of parallel fiber-like beams with the microinjection of glutamate into the upper molecular layer in the presence of DTX-K. The dramatic effects of DTX-K suggest a possible connection between SAD and episodic ataxia type 1 (EA1), a Kv1.1 potassium channelopathy. The threshold for evoking SAD was significantly lowered in the Kv1.1 heterozygous knockout mouse compared with wild-type littermates. Carbamazepine and acetazolamide, both effective in the treatment of EA1, significantly decreased the likelihood of evoking SAD. Blocking GABAergic neurotransmission did not alter the effectiveness of DTX-K. The cyclin D2 null mouse, which lacks cerebellar stellate cells, also exhibited SAD. Therefore blocking Kv1 potassium channels establishes the conditions needed to generate SAD. Furthermore, the results are consistent with the hypothesis that SAD may underlie the transient attacks of ataxia characterizing EA1.

Interaction of GABA and glutamate in the horizontal limb of diagonal band of Broca (hDB): role in cardiovascular responses

The diagonal band of Broca (DBB) is a part of the limbic system that consists of two parts: the vertical limb (vDB) and the horizontal limb (hDB). It has been shown that microinjection of glutamate into the hDB of the anesthetized rat elicited depressor responses. We have previously shown that microinjection of AP5 (an NMDA receptor antagonist, 2.5 mM, 50 nl) and CNQX (an AMPA receptor antagonist, 1 mM, 50 nl) caused no significant changes in the blood pressure and heart rate. Microinjection of bicuculline (BMI: a GABA A receptor antagonist, 1 mM, 50 nl) resulted in the increase of both the blood pressure and heart rate. In this study, we investigated the possible interaction of the GABAergic and glutaminergic systems of the hDB by coinjection of the antagonists of both systems. Experiments were performed on the 24 urethane-anesthetized rats. Repeated measures ANOVA was used for data analysis. Our results showed that coinjection of 50 nl of 1 mM of BMI and 2.5 mM of AP5 significantly (ANOVA, P < 0. 01) decreased the pressor effects of BMI. Also, coinjection of 50 nl of BMI (1 mM) and CNQX (1 mM) significantly (ANOVA, P < 0.01) decreased the pressor effects of BMI. Coinjection of the previous amounts of BMI and both of the glutamate receptor antagonists also produced the same results. These results showed that the cardiovascular effects of blockade of GABAergic inhibition in the hDB are dependent on the activation of local NMDA and non-NMDA receptors of glutamate. A possible interpretation of the results is that, the GABAergic neurons inhibit the glutaminergic neurons.

Striatal Inhibition of Nociceptive Responses Evoked in Trigeminal Sensory Neurons by Tooth Pulp Stimulation

The noxious evoked response in trigeminal sensory neurons was studied to address the role of striatum in the control of nociceptive inputs. In urethane-anesthetized rats, the jaw opening reflex (JOR) was produced by suprathreshold stimulation of the tooth pulp and measured as electromyographic response in the digastric muscle, with simultaneous recording of noxious responses in single unit neurons of the spinal trigeminal nucleus pars caudalis (Sp5c). The microinjection of glutamate (80 etamol/0.5 microl) into striatal JOR inhibitory sites significantly decreased the A delta and C fiber-mediated-evoked response (53 +/- 4.2 and 43.6 +/- 6.4% of control value, P < 0.0001) in 92% (31/34) of nociceptive Sp5c neurons. The microinjection of the solvent was ineffective, as was microinjection of glutamate in sites out of the JOR inhibitory ones. In another series of experiments, simultaneous single unit recordings were performed in the motor trigeminal nucleus (Mo5) and the Sp5c nucleus. Microinjection of glutamate decreased the noxious-evoked response in Sp5c and Mo5 neurons in parallel with the JOR, without modifying spontaneous neuronal activity of trigeminal motoneurons (n = 8 pairs). These results indicate that the striatum could be involved in the modulation of nociceptive inputs and confirm the role of the basal ganglia in the processing of nociceptive information.

The medial amygdaloid area is involved in activation of angiotensin II-sensitive neurons in the anterior hypothalamic area

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that the activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats. It is suggested that there exist neural projections from the medial amygdala to the AHA in rats. In this study, we examined whether neurons in the medial amygdaloid area (MeA) are involved in the activation of AHA angiotensin II-sensitive neurons. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of glutamate into the MeA caused an increase in the firing rate of AHA angiotensin II-sensitive neurons. The glutamate-induced increase of firing rate was inhibited by pressure application of the AT1 receptor antagonist losartan onto AHA angiotensin II-sensitive neurons. The microinjection of glutamate into the central amygdaloid area also increased the firing rate of AHA angiotensin II-sensitive neurons, but the glutamate-induced increase of firing rate was not affected by pressure application of losartan onto AHA angiotensin II-sensitive neurons. The microinjection of corticotropin-releasing factor (CRF) into the MeA also increased the firing rate of AHA angiotensin II-sensitive neurons, but the CRF-induced increase of firing rate was not inhibited by pressure application of losartan onto AHA angiotensin II-sensitive neurons. Repeated microinjection of glutamate into the MeA caused an increase in the release of angiotensins in the AHA. These findings indicate that neurons in the MeA are involved in the activation of AHA angiotensin II-sensitive neurons. It seems likely that the activation of AHA angiotensin II-sensitive neurons induced by glutamate but not CRF is partly mediated via the release of angiotensins at AHA angiotensin II-sensitive neuron levels.

Abstracts

Abstracts

Involvement of Ventral Pallidum in Prefrontal Cortex-Dependent Aspects of Spatial Working Memory.

Ventral pallidum (VP) is an important source of limbic input to medial thalamus. Three studies examined the role of VP in spatial memory tasks impaired by medial thalamic lesions. In the 1st study, rats with VP lesions were impaired performing delayed matching trained with retractable levers (DMRL), a measure sensitive to prefrontal (but not hippocampal) damage. The 2nd study demonstrated dose-dependent DMRL impairment following microinjection of gamma-aminobutyric acidA, glutamate, or mu-opioid agonists in VP. In the 3rd study, VP lesions had no effect on varying choice radial-maze delayed nonmatching, a measure sensitive to hippocampal (but not prefrontal) lesions. These results suggest a common role in spatial memory for VP and other components of prefrontal-ventral striatopallidothalamic circuits distinct from hippocampal function.