Lateral Septal Area Research Articles

Lifespan changes in cannabinoid 1 receptor mRNA expression in the female C57BL/6J mouse brain.

Many brain functions that underlie behavior, cognition, and emotions vary with age, as does susceptibility to neuropsychological disorders. The expression of specific genes that are involved in these functions, such as the genes encoding for oxytocin, its receptors, and apolipoprotein D, varies with age across different brain regions. The cannabinoid 1 receptor (CB1 R) is one of the most widely spread G-protein coupled receptors in the central nervous system and is increasingly recognized for its important contribution to various brain functions. Although changes in CB1 R expression with age have been reported in the male mouse brain, they have not been well investigated in the female brain. Here, we used fluorescence in situ hybridization to target CB1 R mRNA in the whole brains of female C57BL/6J mice aged 4, 6, 12, 52 (12 months) and 86weeks (20 months), and quantified CB1 R-positive cells in 36 brain regions across the whole brain. The results showed that CB1 R-positive cells number changed with age. Specifically, CB1 R expression increased with age in some subregions of the cortex, decreased with age in the lateral septal area, and reached its lowest level at 52weeks in the thalamus, hypothalamus, and hindbrain subregions. Cluster analysis revealed that some brain regions shared similar temporal characteristics in CB1 R-positive cell number across the lifespan. Our results provide evidence that investigation of the neural basis of age-related characteristics of female brain functions is not only warranted but required.

Neural connectivity between the hypothalamic supramammillary nucleus and appetite‐ and motivation‐related regions of the rat brain

The supramammillary nucleus (SuM) has an emerging role in appetite control. We have shown that the rat SuM is activated during hunger or food anticipation, or by ghrelin administration. In the present study, we characterised the connectivity between the SuM and key appetite‐ and motivation‐related nuclei in the rat. In adult wild‐type rats, or rats expressing Cre recombinase under the control of the tyrosine hydroxylase (TH) promoter (TH‐Cre rats), we used c‐Fos immunohistochemistry to visualise and correlate the activation of medial SuM (SuMM) with activation in the lateral hypothalamic area (LH), the dorsomedial hypothalamus (DMH) or the ventral tegmental area (VTA) after voluntary consumption of a high‐sugar, high‐fat food. To determine neuroanatomical connectivity, we used retrograde and anterograde tracing methods to specifically investigate the neuronal inputs and outputs of the SuMM. After consumption of the food there were positive correlations between c‐Fos expression in the SuMM and the LH, DMH and VTA (P = 0.0001, 0.01 and 0.004). Using Fluoro‐Ruby as a retrograde tracer, we demonstrate the existence of inputs from the LH, DMH, VTA and ventromedial hypothalamus (VMH) to the SuMM. The SuMM showed reciprocal inputs to the LH and DMH, and we identified a TH‐positive output from SuMM to DMH. We co‐labelled retrogradely‐labelled sections for TH in the VMH, or for TH, orexin and melanin‐concentrating hormone in the LH and DMH. However, we did not observe any colocalisation of immunoreactivity with any retrogradely‐labelled cells. Viral mapping in TH‐Cre rats confirms the existence of a reciprocal SuMM‐DMH connection and shows that TH‐positive cells project from the SuMM and VTA to the lateral septal area and cingulate cortex, respectively. These data provide evidence for the connectivity of the SuMM to brain regions involved in appetite control, and form the foundation for functional and behavioural studies aiming to further characterise the brain circuitry controlling eating behaviours.

The Spatial and Temporal Characters of Demyelination and Remyelination in the Cuprizone Animal Model.

Multiple sclerosis (MS) is the most common central nervous system disease due to demyelination in young adults, and currently, there is no cure. Some experimental animal models were generated to mimic specific aspects of MS pathological characteristics. Among them, the cuprizone (CPZ)-induced mouse demyelination model presents heterogeneous pathologies with both focal and diffuse lesions. Considering that MS is a progressive disease, it is important to study the spatial and temporal characters of de- and remyelination in MS animal models. However, such data especially in some brain regions such as lateral septal area, fimbria of hippocampus, and hippocampus are still lacking. In this study, we investigated the alterations of myelin in these areas in parallel to the changes in corpus callosum using coronal sections. We found that the progression of demyelinating varied in different brain regions in C57BL/6J mice treated with CPZ for 1 to 5 weeks. This result suggests that each brain region has a distinct sensitivity to CPZ intoxication. Interestingly, activated microglia appeared not only in the active demyelinating areas but also in the non-myelinolysis regions. After CPZ withdrawal, significant remyelination was started in corpus callosum as early as 3 days. The completion of remyelination in the entire brain regions took 3 weeks. Our study detailed characterized the dynamics of myelin alterations and microglial status in the brain of the CPZ model. This information is valuable to facilitate further MS studies utilizing the CPZ model. Anat Rec, 302:2020-2029, 2019. © 2019 American Association for Anatomy.

Chronic stress and moderate physical exercise prompt widespread common activation and limited differential activation in specific brain regions

Chronic stress in rodents produces depressive behaviors, whereas moderate physical exercise counteracts stress-induced depressive behaviors. Chronic stress and physical exercise appear to produce such opposing effects by changing the neural activity of specific brain regions. However, the detailed mechanisms through which the two different types of stimuli regulate brain function in opposite directions are not clearly understood. In the present study, we attempted to explore the neuroanatomical substrates mediating stress-induced behavioral changes and anti-depressant effects of exercise by examining stimulus-dependent c-Fos induction in the brains of mice that were exposed to repeated stress or exercise in a scheduled manner. Systematic and integrated analyses of c-Fos expression profiles indicated that various brain areas, including the prelimbic cortex, lateral septal area, and paraventricular nuclei of hypothalamus were commonly and strongly activated by both stress and exercise, while the lateral habenula and hippocampus were identified as being preferentially activated by stress and exercise, respectively. Exercise-dependent c-Fos expression in all regions examined in the brain occurred in both glutamatergic and GABAergic neurons. These results suggest that chronic stress and moderate exercise produce counteractive effects on mood behaviors, along with prompting widespread common activation and limited differential activation in specific brain regions.

Cortical network switching: possible role of the lateral septum and cholinergic arousal.

Cortical networks undergo large-scale switching between states of increased or decreased activity in normal sleep and cognition as well as in pathological conditions such as epilepsy. We previously found that focal hippocampal seizures in rats induce increased neuronal firing and cerebral blood flow in subcortical structures including the lateral septal area, along with frontal cortical slow oscillations resembling slow wave sleep. In addition, stimulation of the lateral septum in the absence of a seizure resulted in cortical deactivation with slow oscillations. We hypothesized that lateral septal activation might cause neocortical deactivation indirectly, possibly through impaired subcortical arousal. But how does subcortical stimulation cause slow wave activity in frontal cortex? How do arousal neurotransmitter levels (e.g. acetylcholine) change in cortex during the excitation of inhibitory projection nuclei? In the current study, we used simultaneous electrophysiology and enzyme-based amperometry in a rat model, and found a decrease in choline, along with slow wave activity in orbital frontal cortex during lateral septal stimulation in the absence of seizures. In contrast, the choline signal and local field potential in frontal cortex had no significant changes when stimulating the hippocampus, but showed increased choline and decreased slow wave activity with an arousal stimulus produced by toe pinch. These findings indicate that the activation of subcortical inhibitory structures (such as lateral septum) can depress subcortical cholinergic arousal. This mechanism may play an important role in large-scale transitions of cortical activity in focal seizures, as well as in normal cortical function.

P.1.g.055 5-HT2A/2C serotonergic receptors of lateral septal area modulate fear-induced responses elicited by activation of dorsolateral periaqueductal grey matter

While group 1 metabotropic glutamate receptors (mGluRs) and ionotropic N-methyl-d-aspartate (NMDA) receptors regulate nociception, the precise molecular mechanism(s) contributing to glutamate signaling in chronic pain remain unclear. Here we not only confirmed the key involvement of Homer proteins in neuropathic pain, but also distinguished between the functional roles for different Homer family members and isoforms. Chronic constriction injury (CCI) of the sciatic nerve induced long-lasting, time-dependent increases in the postsynaptic density expression of the constitutively expressed (CC) isoforms Homer1b/c and/or Homer2a/b in the spinal dorsal horn and supraspinal structures involved in nociception (prefrontal cortex, thalamus), that co-occurred with increases in their associated mGluRs, NR2 subunits of the NMDA receptor, and the activation of downstream kinases. Virus-mediated overexpression of Homer1c and Homer2b after spinal (intrathecal) virus injection exacerbated CCI-induced mechanical and cold hypersensitivity, however, Homer1 and Homer2 gene knockout (KO) mice displayed no changes in their neuropathic phenotype. In contrast, overexpression of the immediate early gene (IEG) Homer1a isoform reduced, while KO of Homer1a gene potentiated neuropathic pain hypersensitivity. Thus, nerve injury-induced increases in CC-Homers expression promote pain in pathological states, but IEG-Homer induction protects against both the development and maintenance of neuropathy. Additionally, exacerbated pain hypersensitivity in transgenic mice with reduced Homer binding to mGluR5 supports also an inhibitory role for Homer interactions with mGluR5 in mediating neuropathy. Such data indicate that nerve injury-induced changes in glutamate receptor/Homer signaling contribute in dynamic but distinct ways to neuropathic pain processing, which has relevance for the etiology of chronic pain symptoms and its treatment.

Neuropeptide Y mRNA and peptide in the night-migratory redheaded bunting brain

This study investigated the distribution of neuropeptide Y (NPY) in the brain of the night-migratory redheaded bunting (Emberiza bruniceps). We first cloned the 275-bp NPY gene in buntings, with ≥95% homology with known sequences from other birds. The deduced peptide sequence contained all conserved 36 amino acids chain of the mature NPY peptide, but lacked 6 amino acids that form the NPY signal peptide. Using digosigenin-labeled riboprobe prepared from the cloned sequence, the brain cells that synthesize NPY were identified by in-situ hybridization. The NPY peptide containing cell bodies and terminals (fibers) were localized by immunocytochemistry. NPY mRNA and peptide were widespread throughout the bunting brain. This included predominant pallial and sub-pallial areas (cortex piriformis, cortex prepiriformis, hyperpallium apicale, hippocampus, globus pallidus) and thalamic and hypothalamic nuclei (organum vasculosum laminae terminalis, nucleus (n.) dorsolateralis anterior thalami, n. rotundus, n. infundibularis) including the median eminence and hind brain (n. pretectalis, n. opticus basalis, n. reticularis pontis caudalis pars gigantocellularis). The important structures with only NPY-immunoreactive fibers included the olfactory bulb, medial and lateral septal areas, medial preoptic nucleus, medial suprachiasmatic nucleus, paraventricular nucleus, ventromedial hypothalamic nucleus, optic tectum, and ventro-lateral geniculate nucleus. These results demonstrate that NPY is possibly involved in the regulation of several physiological functions (e.g. daily timing feeding, and reproduction) in the migratory bunting.

Neuroanatomical and neuropharmacological approaches to postictal antinociception‐related prosencephalic neurons: the role of muscarinic and nicotinic cholinergic receptors

Several studies have suggested the involvement of the hippocampus in the elaboration of epilepsy. There is evidence that suggests the hippocampus plays an important role in the affective and motivational components of nociceptive perception. However, the exact nature of this involvement remains unclear. Therefore, the aim of this study was to determine the role of muscarinic and nicotinic cholinergic receptors in the dorsal hippocampus (dH) in the organization of postictal analgesia. In a neuroanatomical study, afferent connections were found from the somatosensory cortex, the medial septal area, the lateral septal area, the diagonal band of Broca, and the dentate gyrus to the dH; all these areas have been suggested to modulate convulsive activity. Outputs to the dH were also identified from the linear raphe nucleus, the median raphe nucleus (MdRN), the dorsal raphe nucleus, and the locus coeruleus. All these structures comprise the endogenous pain modulatory system and may be involved either in postictal pronociception or antinociception that is commonly reported by epileptic patients. dH-pretreatment with cobalt chloride (1.0 mmol/L CoCl2/0.2 μL) to transiently inhibit local synapses decreased postictal analgesia 10 min after the end of seizures. Pretreatment of the dH with either atropine or mecamylamine (1.0 μg/0.2 μL) attenuated the postictal antinociception 30 min after seizures, while the higher dose (5.0 μg/0.2 μL) decreased postictal analgesia immediately after the end of seizures. These findings suggest that the dH exerts a critical role in the organization of postictal analgesia and that muscarinic and nicotinic cholinergic receptor-mediated mechanisms in the dH are involved in the elaboration of antinociceptive processes induced by generalized tonic-clonic seizures.

The medial amygdaloid nucleus is involved in the cardiovascular pathway activated by noradrenaline into the lateral septal area of rats

We have previously reported that noradrenaline (NA) microinjected into the lateral septal area (LSA) caused pressor and bradicardic responses that were mediated by vasopressin release into the circulation through the paraventricular nucleus of hypothalamus (PVN). Although PVN is the final structure involved in the cardiovascular responses caused by NA in the LSA, there is no evidence of direct connections between these areas, suggesting that some structures could be links in this pathway. In the present study, we verified the effect of reversible synaptic inactivation of the medial amygdaloid nucleus (MeA), bed nucleus of stria terminalis (BNST) or diagonal band of Broca (DBB) with Cobalt Chloride (CoCl(2) ) on the cardiovascular response to NA microinjection into the LSA of unanesthetized rats. Male Wistar rats had guide cannulae implanted into the LSA and the MeA, BNST or DBB for drug administration, and a femoral catheter for blood pressure and heart rate recordings. Local microinjection of CoCl(2) (1 mm in 100 nL) into the MeA significantly reduced the pressor and bradycardic responses caused by NA microinjection (21 nmol in 200 nL) into the LSA. In contrast, microinjection of CoCl(2) into the BNST or DBB did not change the cardiovascular responses to NA into the LSA. The results indicate that synapses within the MeA, but not in BNST or DBB, are involved in the cardiovascular pathway activated by NA microinjection into the LSA.

Brain pathways involved in the modulatory effects of noradrenaline in lateral septal area on cardiovascular responses.

We have previously reported that stimulation of alpha-1 adrenoceptors by noradrenaline (NA) injected into the lateral septal area (LSA) of anaesthetized rats causes pressor and bradycardic responses that are mediated by acute vasopressin release into the circulation through activation of the paraventricular nucleus (PVN). Although the PVN is the final structure of this pathway, the LSA has no direct connections with the PVN, suggesting that other structures may connect these areas. To address this issue, the present study employed c-Fos immunohistochemistry to investigate changes caused by NA microinjection into the LSA in neuronal activation in brain structures related to systemic vasopressin release. NA microinjected in the LSA caused pressor and bradycardic responses, which were blocked by intraseptal administration of α-1 adrenoceptor antagonist (WB4101, 10 nmol/200 nL) or systemic V-1 receptor antagonist (dTyr(CH2)5(Me)AVP, 50 μg/kg). NA also increased c-Fos immunoreactivity in the prelimbic cortex (PL), infralimbic cortex (IL), dorsomedial periaqueductal gray (dmPAG), bed nucleus of the stria terminalis (BNST), PVN, and medial amygdala (MeA). No differences in the diagonal band of Broca, cingulate cortex, and dorsolateral periaqueductal gray (dlPAG) were found. Systemic administration of the vasopressin receptor antagonist dTyr AVP (CH2)5(Me) did not change the increase in c-Fos expression induced by intra-septal NA. This latter effect, however, was prevented by local injection of the alpha-1 adrenoceptor antagonist WB4101. These results suggest that areas such as the PL, IL, dmPAG, BNST, MeA, and PVN could be part of a circuit responsible for vasopressin release after activation of alpha-1 adrenoceptors in the LSA.

Lateral septal area α1‐ and α2‐adrenoceptors differently modulate baroreflex activity in unanaesthetized rats

The lateral septal area (LSA) is a limbic structure involved in autonomic, neuroendocrine and behavioural responses. An inhibitory influence of the LSA on baroreflex activity has been reported; however, the local neurotransmitter involved in this modulation is still unclear. In the present study, we verified the involvement of local LSA adrenoceptors in modulating cardiac baroreflex activity in unanaesthetized rats. Bilateral microinjection of the selective α(1)-adrenoceptor antagonist WB4101 (10 nmol in a volume of 100 nl) into the LSA decreased baroreflex bradycardia evoked by blood pressure increases, but had no effect on reflex tachycardia evoked by blood pressure decreases. Nevertheless, bilateral administration of the selective α(2)-adrenoceptor antagonist RX821002 (10 nmol in 100 nl) increased baroreflex tachycardia without affecting reflex bradycardia. Treatment of the LSA with a cocktail containing WB4101 and RX821002 decreased baroreflex bradycardia and increased reflex tachycardia. The non-selective β-adrenoceptor antagonist propranolol (10 nmol in 100 nl) did not affect either reflex bradycardia or tachycardia. Microinjection of noradrenaline into the LSA increased reflex bradycardia and decreased the baroreflex tachycardic response, an opposite effect compared with those observed after double blockade of α(1)- and α(2)-adrenoceptors, and this effect of noradrenaline was blocked by local LSA pretreatment with the cocktail containing WB4101 and RX821002. The present results provide advances in our understanding of the baroreflex neural circuitry. Taken together, data suggest that local LSA α(1)- and α(2)-adrenoceptors modulate baroreflex control of heart rate differently. Data indicate that LSA α(1)-adrenoceptors exert a facilitatory modulation on baroreflex bradycardia, whereas local α(2)-adrenoceptors exert an inhibitory modulation on reflex tachycardia.

Behavioral and autonomic responses to acute restraint stress are segregated within the lateral septal area of rats.

BackgroundThe Lateral Septal Area (LSA) is involved with autonomic and behavior responses associated to stress. In rats, acute restraint (RS) is an unavoidable stress situation that causes autonomic (body temperature, mean arterial pressure (MAP) and heart rate (HR) increases) and behavioral (increased anxiety-like behavior) changes in rats. The LSA is one of several brain regions that have been involved in stress responses. The aim of the present study was to investigate if the neurotransmission blockade in the LSA would interfere in the autonomic and behavioral changes induced by RS.Methodology/Principal FindingsMale Wistar rats with bilateral cannulae aimed at the LSA, an intra-abdominal datalogger (for recording internal body temperature), and an implanted catheter into the femoral artery (for recording and cardiovascular parameters) were used. They received bilateral microinjections of the non-selective synapse blocker cobalt chloride (CoCl2, 1 mM/ 100 nL) or vehicle 10 min before RS session. The tail temperature was measured by an infrared thermal imager during the session. Twenty-four h after the RS session the rats were tested in the elevated plus maze (EPM).Conclusions/SignificanceInhibition of LSA neurotransmission reduced the MAP and HR increases observed during RS. However, no changes were observed in the decrease in skin temperature and increase in internal body temperature observed during this period. Also, LSA inhibition did not change the anxiogenic effect induced by RS observed 24 h later in the EPM. The present results suggest that LSA neurotransmission is involved in the cardiovascular but not the temperature and behavioral changes induced by restraint stress.

Alpha2 but not alpha1 and beta adrenoceptors in the lateral septal area modulates cardiovascular responses evoked by restraint stress in rats

s / Autonomic Neuroscience: Basic and Clinical 163 (2011) 1–133 57 P.042 Alpha2 but not alpha1 and beta adrenoceptors in the lateral septal area modulates cardiovascular responses evoked by restraint stress in rats A.A. Scopinho, D.G. Reis, L.B.M. Resstel, F.M.A. Correa (Faculdade de Medicina de Ribeirao Preto, USP Farmacologia, Brazil) Background/aims: The lateral septal area (LSA) is involved in cardiovascular responses connected with emotional behavior. Restraint stress (RS) causes hypertension and tachycardia, and these responses are significantly reduced by microinjection of cobalt chloride (inhibitor synaptic) in LSA. RS also causes increased expression of c-fos in ASL, suggesting that this structure is involved in the modulation of cardiovascular responses evoked by the RS. Microdialysis studies showed that the levels of noradrenaline (NA) are increased during RS in several limbic regions involved in behavioral and autonomic responses, including LSA. Then, the aim of our study was to investigate the involvement of the noradrenergic system of ASL on the cardiovascular responses caused by the RS. Methods: Wistar rats were used (240-280 g). Guide-cannulae were implanted bilaterally in the LSA for microinjection of alpha2-receptor antagonist RX821002 (10 nmol/100 nL), alpha1-receptor antagonist WB4101 (10 nmol/100 nL), beta receptor antagonist propranolol (10 nmol/100 nL) or vehicle artificial cerebrospinal fluid (aCSF). A catheter was implanted in the femoral artery to record arterial pressure and heart rate. Ten minutes after the microinjection of drugs, the animals were submitted to the RS for an hour. Results: Acute restraint caused significant increases in both MAP (F35,360=5.2; P<0.001) and HR (F35,360=7.56; P<0.001). RX821002 treatment significantly reduced the MAP increase (F1,360=32.66, P<0.0001) and tachycardiac response (F1,350=84.96, P<0.0001) evoked by RS. In contrast, WB4101 did not change the MAP increase (F1,280=2.1; P=0,1452) and tachycardia (F1,280=0.68; P=0,4091) evoked by RS. Also, propranolol did not change the MAP increase (F1,315=3.5; P=0,0589) and tachycardia (F1,315=2.9; P=0,0853) evoked by RS. Conclusion: These results suggest that noradrenergic alpha2adrenoceptors in the LSA has facilitatory role in controlling cardiovascular responses to RS. Moreover, alpha1 and beta adrenoceptors do not seem to be involved in these responses.

On a possible dual role for the lateral septal area 5-HT 1A receptor system in the regulation of water intake and urinary excretion

The 5-hydroxytryptamine (5-HT) 1A receptor system plays a prominent role in a variety of physiological functions and behavior and regulation of this responsiveness of the receptor system has been implicated in the central regulation of water intake and urinary excretion. The lateral septal area (LSA) exhibits a high density of 5-HT 1A receptors, as well as a subpopulation of oxytocin (OT) receptors. Here we report the effects of pMPPF (a selective 5-HT 1A antagonist), d(CH 2) 5[Tyr(Me) 2Thr 4, Orn 5, Tyr(NH 2) 9]-vasotocin (an OT antagonist), and that 5-HT 1A receptor system is regulated as a consequence of activation of the Na + channel by veratridine. Cannulae were implanted into the LSA of rats to enable the introduction of the drugs. Injections of 8-OH-DPAT (a 5-HT 1A agonist) blocked water intake and increased urinary excretion, while pMPPF or the OT antagonist injected bilaterally before 8-OH-DPAT blocked its inhibitory effect on water intake and its diuretic effect. In contrast, increases in extracellular sodium levels induced by the sodium channel modulator, veratridine, enhanced 5-HT 1A responsiveness for water intake and reduced the diuretic effects induced by 8-OH-DPAT. These trials demonstrated that the responsiveness of the 5-HT 1A receptor system in the LSA can be enhanced or depressed as a consequence of an induced rise in extracellular sodium.

Involvement of the lateral septal area in the expression of fear conditioning to context

Considering the evidence that the lateral septal area (LSA) modulates defensive responses, the aim of the present study is to verify if this structure is also involved in contextual fear conditioning responses. Neurotransmission in the LSA was reversibly inhibited by bilateral microinjections of cobalt chloride (CoCl(2), 1 mM) 10 min before or after conditioning or 10 min before re-exposure to the aversively conditioned chamber. Only those animals that received CoCl(2) before re-exposure showed a decrease in both cardiovascular and behavioral conditioned responses. These results suggest that the LSA participates in the expression, but not acquisition or consolidation, of contextual fear conditioning.

Role of serotonergic 5-HT 1A and oxytocinergic receptors of the lateral septal area in sodium intake regulation

Several reports have revealed a high density of 5-HT 1A receptors in the lateral septal area (LSA), as well as a subpopulation of oxytocin (OT) receptors. Increasing evidence shows that 5-HT 1A and OT neurons inhibit sodium urinary excretion. The aim of this study was to investigate the part played by serotonergic (5-HT 1A) and oxytocinergic receptors in the LSA in the sodium intake induced in rats by sodium depletion followed by 24 h deprivation. Cannulae were implanted bilaterally into the LSA of rats to enable the introduction of receptor ligands into that brain area. Serotonergic injections of 5-HT (10, 20, and 40 μg/0.2 μL) reduced 1.8% NaCl solution intake, but injections (1, 2, and 4 μg/0.2 μL) of 8-OH-DPAT, a 5-HT 1A agonist, were more effective than 5-HT in reducing 1.8% NaCl intake. Pretreatment of the LSA with the 5-HT 1A antagonist pMPPF partially reduced the inhibitory effect of 5-HT and totally reversed the effects of 8-OH-DPAT on 1.8% NaCl intake induced by sodium depletion. Previous treatment with the potent oxytocin receptor antagonist d(CH 2) 5[Tyr(Me) 2Thr 4, Orn 5, Tyr(NH 2) 9]-vasotocin also totally blocked the inhibitory effects of 5-HT or 8-OH-DPAT on 1.8% NaCl intake. These results show that 5-HT 1A serotonergic receptors in the LSA, including some that interact with the oxytocinergic system, modulate sodium intake induced by sodium loss in rats.

Involvement of the intermediate nucleus of the lateral septal area on angiotensin II-induced dipsogenic and pressor responses

Previous studies have shown that different parts of the septal area may have opposite roles in the control of water intake and cardiovascular responses. In the present study we investigated the effects of electrolytic lesions of the intermediate nucleus of the lateral septal area (LSI) on cardiovascular and dipsogenic responses to intracerebroventricular (icv) angiotensin II (ANG II) and water intake induced by other different stimuli. Male Holtzman rats (280–320 g of body weight, n = 6–16/group) with sham or electrolytic lesions of the LSI and a stainless steel cannula implanted into the lateral ventricle (LV) were used. The LSI lesions did not affect body weight or daily water intake. However, LSI lesions reduced water intake and pressor responses induced by icv ANG II (4.10 − 2 nmol). The LSI lesions also slightly reduced water intake induced by 24 h of water deprivation or isoproterenol (30 μg/kg) subcutaneously, but did not affect water intake induced by intragastric 2 ml of 2 M NaCl load. The results suggest that LSI is part of the forebrain circuitry activated by ANG II to produce pressor and dipsogenic responses. However, the same nucleus is not involved in the dipsogenic responses to central osmoreceptor activation.

The medial nucleus of amygdala (MeA) mediate the cardiovascular responses evoked by noradrenaline microinjected into the lateral septal area (LSA) in rats

IntroductionWe demonstrated that the microinjection of noradrenaline into the LSA evoked pressor and bradycardic responses mediated by vasopressin release. Moreover, the microinjection of cobalt or selective non‐NMDA antagonist NBQX into the paraventricular nucleus (PVN) blocked the pressor response and bradycardia evoked by NA injected into the LSA, suggesting the PVN as the final structure in this pathway. Anatomical dates demonstrated that no direct connections were observed between the LSA and the PVN or the SON. The MeA is a structure involved in cardiovascular control. Projections from the LS to the MeA have also been described in the literature and MeA sends projections to PVN.ObjectiveTo investigate if MeA acute ablation by the injection of cobalt blocked the cardiovascular responses to NA microinjection into the LSA.Methods and ResultsMale Wistar rats were used. Cannulaes was implanted in the LSA and the ipsilaterally in the MeA using a stereotaxic apparatus A catheter was implanted into the femoral artery for blood pressure and heart rate recording. The microinjection of cobalt into the MeA blocked the pressor and bradycardiac responses evoked by NA microinjection into the LSA.ConclusionOur results suggest that synapses in the MeA are involved in the mediation of the pressor and bradycardiac response to the microinjection of NA into the LSA.Financial SupportCAPES and FAEPA.

Non‐N‐methyl‐D‐aspartate glutamate receptors in the paraventricular nucleus of hypothalamus mediate the pressor response evoked by noradrenaline microinjected into the lateral septal area in rats

The lateral septal area (LSA) is a part of the limbic system and is involved in cardiovascular modulation. We previously reported that microinjection of noradrenaline (NA) into the LSA of unanesthetized rats caused pressor responses that are mediated by acute vasopressin release. Magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) of the hypothalamus synthesize vasopressin. In the present work, we studied which of these nuclei is involved in the pressor pathway activated by unilateral NA injection into the LSA as well as the local neurotransmitter involved. Chemical ablation of the SON by unilateral injection of the nonspecific synapses blocker cobalt chloride (1 mM/100 nl) did not affect the pressor response evoked by NA (21 nmol/200 nl) microinjection into the LSA. However, the response to NA was blocked when cobalt chloride (1 mM/100 nl) was microinjected into the PVN, indicating that this hypothalamic nucleus is responsible for the mediation of the pressor response. There is evidence in the literature pointing to glutamate as a putative neurotransmitter activating magnocellular neurons. Pretreatment of the PVN with the selective non-N-methyl-D-asparate (NMDA) antagonist NBQX (2 nmol/100 nl) blocked the pressor response to NA microinjected into the LSA, whereas pretreatment with the selective NMDA antagonist LY235959 (2 nmol/100 nl) did not affect the response to NA. Our results implicate the PVN as the final structure in the pressor pathway activated by the microinjection of NA into the LSA. They also indicate that local glutamatergic synapses and non-NMDA glutamatergic receptors mediate the response in the PVN.

Vasopressin modulates lateral septal network activity via two distinct electrophysiological mechanisms

The lateral septal area is rich in vasopressin V(1A) receptors and is densely innervated by vasopressinergic axons, originating mainly from the bed nucleus of the stria terminalis and the amygdala. Genetic and behavioral studies provide evidence that activation of vasopressin receptors in this area plays a determinant role in promoting social recognition. What could be the neuronal mechanism underlying this effect? Using rat brain slices and whole-cell recordings, we found that lateral septal neurons are under the influence of a basal GABAergic inhibitory input. Vasopressin, acting via V(1A) but not V(1B) receptors, greatly enhanced this input in nearly all neurons. The peptide had no effect on miniature inhibitory postsynaptic currents, indicating that it acted on receptors located in the somatodendritic membrane, rather than on axon terminals, of GABAergic interneurons. Cell-attached recordings showed that vasopressin can cause a direct excitation of a subpopulation of lateral septal neurons by acting via V(1A) but not V(1B) receptors. The presence in the lateral septum of V(1A) but not of V(1B) receptors was confirmed by competition binding studies using light microscopic autoradiography. In conclusion, vasopressin appears to act in the lateral septum in a dual mode: (i) by causing a direct excitation of a subpopulation of neurons, and (ii) by causing an indirect inhibition of virtually all lateral septal neurons. This modulation by vasopressin of the lateral septal circuitry may be part of the neuronal mechanism by which the peptide, acting via V(1A) receptors, promotes social recognition.