Septal Rats Research Articles

Alterations in hippocampal cholinergic dynamics following CRF infusions into the medial septum of male and female rats

Corticoptropin releasing factor (CRF) is implicated in stress-related physiological and behavioral changes. The septohippocampal pathway regulates hippocampal-dependent mnemonic processes, which are affected in stress-related disorders, and given the abundance of CRF receptors in the medial septum (MS), this pathway is influenced by CRF. Moreover, there are sex differences in the MS sensitivity to CRF and its impact on hippocampal function. However, the mechanisms underlying these associations remain elusive. In the present study, we utilized an in vivo biosensor-based electrochemistry approach to examine the impact of MS CRF infusions on hippocampal cholinergic signaling dynamics in male and female rats. Our results show increased amplitudes of depolarization-evoked phasic cholinergic signals in the hippocampus following MS infusion of CRF at the 3 ng dose as compared to the infusion involving artificial cerebrospinal fluid (aCSF). Moreover, a trend for a sex × infusion interaction indicated larger cholinergic transients in females. On the contrary, intraseptal infusion of a physiologically high dose (100 ng) of CRF produced a subsequent reduction in phasic cholinergic transients in both males and females. The assessment of tonic cholinergic activity over 30 min post-infusion revealed no changes at the 3 ng CRF dose in either sex, but a significant infusion × sex interaction indicated a reduction in females at the 100 ng dose of CRF as compared to the aCSF. Taken together, our results show differential, dose-dependent modulatory effects of MS CRF on the dynamics of phasic and tonic modes of cholinergic signaling in the hippocampus of male and female rats. These cholinergic signaling modes are critical for memory encoding and maintaining arousal states, and may underlie sex differences in cognitive vulnerability to stress and stress-related psychiatric disorders.

Selective Medial Septum Lesions in Healthy Rats Induce Longitudinal Changes in Microstructure of Limbic Regions, Behavioral Alterations, and Increased Susceptibility to Status Epilepticus

Septo-hippocampal pathway, crucial for physiological functions and involved in epilepsy. Clinical monitoring during epileptogenesis is complicated. We aim to evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals’ behavior and susceptibility to establishing a pilocarpine-induced status epilepticus. Male Sprague–Dawley rats were injected into the MS with vehicle or saporins (to deplete GABAergic or cholinergic neurons; n = 16 per group). Thirty-two animals were used for diffusion tensor imaging (DTI); scanned before surgery and 14 and 49 days post-injection. Fractional anisotropy and apparent diffusion coefficient were evaluated in the fimbria, dorsal hippocampus, ventral hippocampus, dorso-medial thalamus, and amygdala. Between scans 2 and 3, animals were submitted to diverse behavioral tasks. Stainings were used to analyze tissue alterations. Twenty-four different animals received pilocarpine to evaluate the latency and severity of the status epilepticus 2 weeks after surgery. Additionally, eight different animals were only used to evaluate the neuronal damage inflicted on the MS 1 week after the molecular surgery. Progressive changes in DTI parameters in both white and gray matter structures of the four evaluated groups were observed. Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Histologically, the GABAergic toxin also induced aberrant mossy fiber sprouting, tissue damage, and neuronal death. Regarding the pilocarpine-induced status epilepticus, this agent provoked an increased mortality rate. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development.

Cholinergic modulation of rearing in rats performing a spatial memory task.

Spatial memory encoding depends in part on cholinergic modulation. How acetylcholine supports spatial memory encoding is not well understood. Prior studies indicate that acetylcholine release is correlated with exploration, including epochs of rearing onto hind legs. Here, to test whether elevated cholinergic tone increases the probability of rearing, we tracked rearing frequency and duration while optogenetically modulating the activity of choline acetyltransferase containing (i.e., acetylcholine producing) neurons of the medial septum in rats performing a spatial working memory task (n= 17 rats). The cholinergic neurons were optogenetically inhibited using halorhodopsin for the duration that rats occupied two of the four open arms during the study phase of an 8-arm radial arm maze win-shift task. Comparing rats' behaviour in the two arm types showed that rearing frequency was not changed, but the average duration of rearing epochs became significantly longer. This effect on rearing was observed during optogenetic inhibition but not during sham inhibition or in rats that received infusions of a fluorescent reporter virus (i.e., without halorhodopsin; n= 6 rats). Optogenetic inhibition of cholinergic neurons during the pretrial waiting phase had no significant effect on rearing, indicating a context-specificity of the observed effects. These results are significant in that they indicate that cholinergic neuron activity in the medial septum is correlated with rearing not because it motivates an exploratory state but because it contributes to the processing of information acquired while rearing.

Distribution and morphology of calcitonin gene-related peptide (CGRP) innervation in flat mounts of whole rat atria and ventricles

Calcitonin gene-related peptide (CGRP) is widely used as a marker for nociceptive afferent axons. However, the distribution of CGRP-IR axons has not been fully determined in the whole rat heart. Immunohistochemically labeled flat-mounts of the right and left atria and ventricles, and the interventricular septum (IVS) in rats for CGRP were assessed with a Zeiss imager to generate complete montages of the entire atria, ventricles, and septum, and a confocal microscope was used to acquire detailed images of selected regions. We found that 1) CGRP-IR axons extensively innervated all regions of the atrial walls including the sinoatrial node region, auricles, atrioventricular node region, superior/inferior vena cava, left pre-caval vein, and pulmonary veins. 2) CGRP-IR axons formed varicose terminals around individual neurons in some cardiac ganglia but passed through other ganglia without making appositions with cardiac neurons. 3) Varicose CGRP-IR axons innervated the walls of blood vessels. 4) CGRP-IR axons extensively innervated the right/left ventricular walls and IVS. Our data shows the rather ubiquitous distribution of CGRP-IR axons in the whole rat heart at single-cell/axon/varicosity resolution for the first time. This study lays the foundation for future studies to quantify the differences in CGRP-IR axon innervation between sexes, disease models, and species.

Effects of berberine hydrochloride on left ventricular structure and function in rats with myocardial hypertrophy

Background Inhibition of Rho/ROCK signalling pathway related proteins can alleviate left ventricular hypertrophy. Berberine hydrochloride (BBR) can effectively inhibit left ventricular hypertrophy. The purpose of this study is to explore the relationship between BBR and Rho/ROCK signalling pathway. Methods Isoproterenol (ISO) was used to induce left ventricular hypertrophy in rats. Two-dimensional speckle tracking technique (2D-STE) was used to evaluate rats in each group (group A: normal control group; Group B: isoproterenol model group; Group C: ISO + 5mg/kg BBR group; Group D: ISO + 10mg/kg BBR group) Heart structure and systolic function. HE staining and Masson staining were used to observe the pathological changes in four groups of rats. The expression levels of RhoA, ROCK-1, TGF-β1 and PTEN protein in myocardial tissues were detected by immunohistochemistry. Result The interventricular septum (IVS) of rats in groups C and D was thinner than that in group B (4.05 ± 0.16 mm vs. 3.50 ± 0.29 mm vs. 4.41 ± 0.23 mm, respectively, p < 0.05), and the global radial strain (GRS) of rats in groups C and D was higher than that in group B, especially in group D (26.05 ± 1.41 vs. 30.64 ± 1.63 vs. 19.40 ± 1.05, respectively, p < 0.05). Compared with group B, the expression levels of RhoA, ROCK-1 and TGF-β1 in groups C and D decreased, while the expression level of PTEN increased, especially in group D (all p < 0.05). Conclusion BBR can improve the cardiac structure and systolic function of rats with left ventricular hypertrophy, and the improvement mechanism may be related to Rho/ROCK signalling pathway.

Optogenetic modulation of hippocampal oscillations ameliorates spatial cognition and hippocampal dysrhythmia following early-life seizures

There is increasing human and animal evidence that brain oscillations play a critical role in the development of spatial cognition. In rat pups, disruption of hippocampal rhythms via optogenetic stimulation during the critical period for memory development impairs spatial cognition. Early-life seizures are associated with long-term deficits in spatial cognition and aberrant hippocampal oscillatory activity. Here we asked whether modulation of hippocampal rhythms following early-life seizures can reverse or improve hippocampal connectivity and spatial cognition. We used optogenetic stimulation of the medial septum to induce physiological 7 Hz theta oscillations in the hippocampus during the critical period of spatial cognition following early-life seizures.Optogenetic stimulation of the medial septum in control and rats subjected to early-life seizures resulted in precisely regulated frequency-matched hippocampal oscillations. Rat pups receiving active blue light stimulation performed better than the rats receiving inert yellow light in a test of spatial cognition. The improvement in spatial cognition in these rats was associated with a faster theta frequency and higher theta power, coherence and phase locking value in the hippocampus than rats with early-life seizures receiving inert yellow light. These findings indicate that following early life seizures, modification of hippocampal rhythms may be a potential novel therapeutic modality.

Deleterious effect in endothelin receptor–mediated coronary artery smooth muscle contractility in high-salt diet rats

Background and aimsHigh-salt diet has been suggested to increase the risk of heart disease. However, the mechanisms underlying coronary artery tension dysfunction caused by high-salt diet are unclear. Previous studies have shown that coronary artery spasm is often induced by endothelin-1 (ET-1) and thromboxane, leading to myocardial ischemia, while the store-operated Ca2+ entry (SOCE) function of coronary smooth muscle is very important in this process. Methods and resultsTension measurements of endothelium-denuded coronary artery ring segments showed that vasocontraction induced by U46619, ET-1, orSTIM1/Orai1-mediated SOCE was significantly lower in 4% high-salt diet rats than in control rats fed a regular diet. The results of western blotting and immunohistochemistry assays showed lower expression levels of endothelial receptors ETA and ETB, STIM1 and Orai1 in coronary artery of high-salt intake rats compared with control rats. Fibrosis was observed by using Masson's trichrome staining and picrosirius red staining. The plasma ET-1 concentration in high-salt diet rats was significantly higher than that of controls. The interventricular septum and posterior wall of high-salt diet rats were significantly thickened. ConclusionOur findings indicated that coronary artery tension was significantly decreased in 4% high-salt diet rats and that this decrease may be due to the change of endothelin receptor and its downstream pathway SOCE related protein expression in coronary artery. Coronary fibrosis was observed in rats fed with high-salt diet. This study provides potential mechanistic insights into high-salt intake–induced heart disease.

Neuroprotective effects of the Chrysophyllum perpulchrum extract against an Alzheimer-like rat model of β amyloid1-40 intrahippocampal injection.

ObjectiveAlzheimer’s disease (AD) is a threatening disease for African populations in the upcoming years because of the increase in their expectancy of life. Here, we investigated whether natural products from Chrysophyllum perpulchrum as catechin and two dimeric procyanidins (catechin + hexose) could prevent progression of oxidative stress and cognitive changes using an AD-like rat model induced by Aβ1-40 injection into the hippocampal CA1 subfield.MethodologyAdult male Wistar rats were either microinjected with 1% ammonia as a vehicle (10 µL) or aggregated Aβ1-40 at 10 µg bilateral hippocampus. On the 14th day of post-surgery, some Aβ rats were treated with melatonin (10 mg/kg i.p.) or with the Chrysophyllum perpulchrum extract (300 mg/kg p.o.), and some sham-operated rats received the extract alone. Cognitive abilities were tested with Y-maze, object recognition test and Morris Water Maze. Oxidative stress markers as well as the level of activated microglial cells were assayed in the brain.ResultsAβ rats exhibited significant deficits of recognition memory and spatial learning. This was associated with an increase of microglia Iba 1 immunoreactivity as well as nitric oxide (NO), malondialdehyde and superoxide dismutase levels but not to the thiol content in the hippocampus, prefrontal cortex and septum of AD-like rats. The Chrysophyllum perpulchrum extract treatment mitigated Aβ-induced cognitive impairments and reversed microglia overactivation and subsequent generation of oxidative stress markers. Interestingly, the neuroprotective actions of the Chrysophyllum perpulchrum extract seem to be comparable to the control drug melatonin used albeit with some more beneficial effects.ConclusionThese findings are preliminary and should be strengthened by more pharmacological studies of bioactive compounds of Chrysophyllum perpulchrum before being proposed as a promising drug against AD.

P.0133 Age-related changes in neurotransmitter markers in the medial septum and hippocampus in rats: relationship with memory impairment

P.0133 Age-related changes in neurotransmitter markers in the medial septum and hippocampus in rats: relationship with memory impairment

Effect of acute alcohol intoxication on scale-free neural activity in the lateral septum in rats

Electrophysiological recordings of brain activity show both oscillatory dynamics that typically are analyzed in the time-frequency domain to describe brain oscillatory phenomena and scale-free arrhythmic activity defined as neural noise. Recent studies consider this arrhythmic fractal dynamics of neural noise as a sensitive biomarker of a number of cognitive processes, activity of neurotransmitter systems, changes that accompany neurodegenerative and psychiatric disorders including alcohol use disorder. We tested the changes in neural noise induced by acute alcohol intoxication in the lateral septum for the entire spectrum (1–200 Hz) of local field potential signal and for frequency specific ranges (delta, theta, beta, gamma and epsilon bands). Five male Wistar rats were implanted with intracranial electrodes and local field potential signal was measured for baseline activity and activity induced by acute ethanol intoxication (2 g/kg). Change in neural noise dynamics was assessed as a change in the slope of linear regression fit of power spectral density curves in double logarithmic scale. In our study alcohol resulted in lower incline of scale-free activity in the lateral septum for high frequency range and for the whole spectrum, which is interpreted generally as increase in neural noise and change in neuronal processing in a more stochastic way initiated by the acute alcohol intoxication. At the same time, we observed decrease in neural noise for low frequency range. The observed changes may be related to the shift of the excitatory-inhibitory balance towards inhibition and changes in neurotransmission mostly in the GABAergic system. Scale-free activity was sensitive in the conditions of acute alcohol intoxication, therefore to understand its role in alcohol use disorder we need more data and studies on the underlying processes. Future studies should include simultaneous recordings and analysis of arrhythmic dynamics with the oscillatory and multiunit spiking activity in the lateral septum. It can reveal the contribution of different-scale processes in changes driven by acute alcohol intoxication and clarify the specific electrophysiological mechanisms.

Changes in the Time-Domain of Heart Rate Variability and Corticosterone after Surgical Trauma to the Nasal Septum in Rats.

The aim of the work was to study changes in the time range of heart rate variability (HRV) against the background of changes in the concentration of corticosterone in blood plasma in rats after surgical trauma to the nasal septum. Septoplasty was simulated in 30 mature male Wistar rats weighing 210-290 g. ECG was recorded with subsequent analysis of the time domain of HRV, as well as blood sampling to estimate changes in the concentration of corticosterone in the blood plasma was performed. As a result, SDNN significantly increased in comparison with the control on days 2 and 3 (p < 0.001) but decreased on days 4-5 (p < 0.001) and 6 (p < 0.01). rMSSD changed in waves with two irregular peaks on days 1 and 6. SDNN/rMSSD, in comparison with the 1st day of the postoperative period, increased on the 2nd day, continued to increase (p<0.05), and then began to decrease on day 4 (p < 0.01). The total HRV power of was low throughout the postoperative period (p < 0.001), except for day 3, when it was equal to the control data. The increase in the total power index fell on day 3 after the operation (p <0.01), after which its decline was observed again. The concentration of corticosterone in the blood plasma in rats was significantly higher than before (p < 0.001). On postoperative day 2 to 4, its plateau was determined. Simulation of septoplasty leads to changes in the time range of HRV, an increase in the concentration of corticosterone in the blood plasma in rats with its maximum at the time of surgery and 24 h later, and the formation of a "plateau" on postoperative days 2 to 4, which coincides with the changes in HRV.

Changes in sleep-wake cycle after microinjection of agonist and antagonist of endocannabinoid receptors at the medial septum of rats

The role of medial septum in the genesis of slow-wave sleep and the inhibition of rapid eye movement sleep has been established using neurotoxic lesion and chemical stimulation of the medial septum. Intracerebroventricular injection of endocannabinoids (anandamide) decreases wake and increases slow-wave and rapid eye movement sleep in rats. Central cannabinoid (CB1) receptors are localized in the rat medial septum; however, the role of cannabinoid receptors at the medial septum on the regulation of sleep-wakefulness in rats lacks evidence. In this study, we have examined the changes in sleep architecture of 21 male Wistar rats, divided into three groups. Initially, 6 rats were used for dose standardization. Subsequently, one group (n = 6) was microinjected with CB1 receptor agonist, R-(+)-WIN 55,212–2 mesylate salt, the second group (n = 6) received microinjection of CB1 receptor antagonist LY 320,135, and the third group (n = 5) was microinjected with the vehicle, DMSO at the medial septum using stereotaxy. The sleep-wake cycle was recorded using electroencephalogram, electro-oculogram, and electromyogram. Microinjection of CB1 receptor agonist at the medial septum decreased slow-wave sleep and increased total sleep time. The increase in total sleep time was due to an increased percentage of rapid eye movement sleep. After the third and fourth hour of CB1 receptor antagonist microinjection at the medial septum, slow-wave sleep decreased when compared to vehicle injection, while rapid eye movement sleep decreased compared to baseline. We conclude that the endocannabinoid system at the septal nucleus acts through CB1 receptors to increase rapid eye movement sleep in rats.

Cholinergic Dysfunction Involvement in Chronic Cerebral Hypoperfusion-Induced Impairment of Medial Septum-dCA1 Neurocircuit in Rats.

Chronic cerebral hypoperfusion (CCH) is considered a preclinical condition of mild cognitive impairment and thought to precede dementia. However, as the principal cholinergic source of hippocampus, whether the septo-hippocampal neurocircuit was impaired after CCH is still unknown. In this study, we established the CCH rat model by bilateral common carotid artery occlusion (2VO). Under anesthesia, the medial septum (MS) of rats was stimulated to evoke the field excitatory post-synaptic potential (fEPSP) in the pyramidal cell layer of dCA1. Consequently, we observed decreased amplitude of fEPSP and increased paired-pulse ratio (PPR) after 8-week CCH. After tail pinch, we also found decreased peak frequency and shortened duration of hippocampal theta rhythm in 2VO rats, indicating the dysfunction of septo-hippocampal neurocircuit. Besides, by intracerebroventricularly injecting GABAergic inhibitor (bicuculline) and cholinergic inhibitors (scopolamine and mecamylamine), we found that CCH impaired both the pre-synaptic cholinergic release and the post-synaptic nAChR function in MS–dCA1 circuits. These results gave an insight into the role of CCH in the impairment of cholinergic MS–dCA1 neurocircuits. These findings may provide a new idea about the CCH-induced neurodegenerative changes.

The impact of trauma of the mucous membrane of the nasal septum in rats on behavioral responses and changes in the balance of the autonomic nervous system (pilot study)

The nasal cavity surgery are usually traumatic surgery. Septoplasty leads to reactive inflammation, edema and hypoxemia. In the present study, we study the response of the autonomic nervous system (ANS), its role in changing behavioral reactions, as well as possible mechanisms of impairment of cognitive and adaptive reactions in rats after trauma to the nasal septum mucosa. The nasal septum mucosa was scarified in 10 adult mongrel male rats. The day before surgery and 2 days after surgery animals were tested in the square-shaped “open field” (OF) and electrocardiogram (ECG) in 1 hour before OF. ANS condition was analyzed by the high-frequency component of the heart rate (HF) and the low-frequency component of the heart rate (LF). The correlation of HF & LF with rat behavior in the open field before and after surgery was performed. Simulation of septoplasty in rats provokes a powerful stress response in the form of a sharp imbalance of ANS towards its PNS on the 2 postoperative day. Changes in behavioral and research reactions of rats in OF are manifested in a decrease in research activity, a display of uneasiness, depression-like state, as well as anxiety.

Differences in reward biased spatial representations in the lateral septum and hippocampus.

The lateral septum (LS), which is innervated by the hippocampus, is known to represent spatial information. However, the details of place representation in the LS, and whether this place information is combined with reward signaling, remains unknown. We simultaneously recorded from rat CA1 and caudodorsal lateral septum in rat during a rewarded navigation task and compared spatial firing in the two areas. While LS place cells are less numerous than in hippocampus, they are similar to the hippocampus in field size and number of fields per cell, but with field shape and center distributions that are more skewed toward reward. Spike cross-correlations between the hippocampus and LS are greatest for cells that have reward-proximate place fields, suggesting a role for the LS in relaying task-relevant hippocampal spatial information to downstream areas, such as the VTA.

The Effect of Surgical Trauma in the Nasal Cavity on the Behavior in the Open Field and the Autonomic Nervous System of Rats.

In this article, the effect of surgical damage to the nasal mucosa in rats under the action of general anesthesia was investigated. The motor activity and heart rate variability (HRV) of rats were studied before and 2 days after the surgery. After surgical exposure, motor activity decreased, the time of fading and grooming increased, VLF increased, and HF decreased. Surgical trauma of the nasal septum in rats at the early postoperative stage promotes a pronounced stress response in the form of a sharp shift in the balance of the autonomic nervous system towards the sympathetic level and causes a decrease in exploratory activity, an anxiety, and a depressive-like state in rats.

Effects of oxytocin receptor antagonism on social function and corticosterone release after adolescent social instability in male rats

Oxytocin influences social behaviour and hypothalamic-pituitary-adrenal (HPA) function. We previously found that social instability stress (SS) from postnatal day 30 to 45 increased oxytocin receptor (OTR) densities in the lateral septum and nucleus accumbens of adolescent male rats. Here, we investigated social behaviour and HPA function in adolescent male SS rats compared with age- and sex-matched controls after intraperitoneal treatment with an OTR antagonist L-368,899 (OTR-A). Regardless of OTR antagonism, adolescent SS rats spent more time in social approach (investigation through wire mesh) but less time in social interaction (physical interaction) with unfamiliar same-sex and same-age peers than did controls. However, OTR-A-treatment caused SS rats to be more socially avoidant than OTR-A-treated controls and saline-treated rats of the same condition. Additionally, the predicted rise in plasma corticosterone in response to OTR-A treatment was blunted in SS rats. Fos immunoreactivity (IR) was used as a marker of neural activation in social brain regions and oxytocin-IR was examined in the paraventricular nucleus of the hypothalamus (PVN) in response to interacting with unfamiliar peers in SS and control rats after OTR-A treatment. OTR-A treatment had little effect on Fos-IR and oxytocin-IR in the analyzed brain regions, but SS rats had lower Fos-IR and oxytocin-IR in the PVN and greater Fos-IR in subregions of the prefrontal cortex, and hippocampus, and lateral septum than did controls. Finally, binding density of OTR was measured in the PVN and hippocampus, and greater OTR binding density was found in the PVN of SS rats. Together, these data demonstrate a greater influence of OTR antagonism on social behaviour and a reduced influence of OTR antagonism on HPA responses after adolescent SS in male rats. The results also suggest that differences in neural functioning in the prefrontal cortex, hippocampus and lateral septum of adolescent SS rats may be involved in their altered social behaviour relative to that of controls.

Place cell firing cannot support navigation without intact septal circuits.

Though it has been known for over half a century that interference with the normal activity of septohippocampal neurons can abolish hippocampal theta rhythmicity, a definitive answer to the question of its function has remained elusive. To clarify the role of septal circuits and theta in location-specific activity of place cells and spatial behavior, three drugs were delivered to the medial septum of rats: Tetracaine, a local anesthetic; muscimol, a GABA-A agonist; and gabazine, a GABA-A antagonist. All three drugs disrupted normal oscillatory activity in the hippocampus. However, tetracaine and muscimol both reduced spatial firing and interfered with the rat's ability to navigate to a hidden goal. After gabazine, location-specific firing was preserved in the absence of theta, but rats were unable to accurately locate the hidden goal. These results indicate that theta is unnecessary for location-specific firing of hippocampal cells, and that place cell activity cannot support accurate navigation when septal circuits are disrupted.

Spatial relationship between the c-Fos distribution and enkephalinergic, substance P, and tyrosine hydroxylase innervation fields after acute treatment with neuroleptics olanzapine, amisulpride, quetiapine, and aripiprazole in the rat septum.

The aim of the present study was to demonstrate the spatial relationship between the c-Fos immunoreactive cells elicited by an acute treatment with neuroleptics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI) and enkephalinergic (ENK), substance P (SP), and tyrosine hydroxylase (TH) innervation fields in the rat septum. Male Sprague Dawley rats received a single injection of OLA (5 mg), ARI (10 mg), AMI (20 mg), QUE (15 mg/kg/b.w.). Ninety min after antipsychotics administration, the animals were transcardially perfused with a fixative and the brains cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black endproduct. Afterwards, the sections were exposed to ENK, SP, and TH antibodies and the reaction product visualized by biotin-labeled fluorescent AlexaFluor 564 dye. The data were evaluated from the sections either simultaneously illuminated with fluorescent and transmission microscope beams or after merging the separately illuminated sections in the Adobe Photoshop 7.0 software. ENK, SP, and TH displayed characteristic spatial images formed by a dense accumulation of immunoreactive fibers and terminals on the both sides of the septum. A dense plexus of axons formed by ENK and SP immunopositive terminals were situated predominantly in the lateral, while TH ones more medial portion of the septum. QUE and AMI activated distinct amount of c-Fos expression in cells located within the SP-immunoreactive principal innervation field. The OLA effect on the c-Fos expression was very pronounced in the ventral TH-labeled principal innervation field including the space between the ENK field ventral portion and the dorsal margin of the accumbens nucleus shell. Generally, the occurrence of c-Fos cells in the ENK-immunoreactive principal innervation field, in comparison with the surrounding septal area, was less abundant after all of the four antipsychotics treatments. The data of the present study indicate that ENK, SP, and TH innervation fields may influence separate populations of septal cells activated by AMI, OLA, QUE, and ARI and that each of these region-differently innervated cells may be associated with the functional heterogeneity of the individual lateral septal nuclei.

The Effects of α1-Adrenoreceptors’ Activation in the Interatrial Septum of Newborn and Adult Rats

Bioelectrical properties of various developing fragments of the heart undergo significant changes during pre- and postnatal ontogeny. However, the general pattern of the heart’s structure and the bioelectrical features of various parts of the “mature” heart are specifically determined in the early stages of embryogenesis. Specifically, the presence of myocardium with a phenotype, which is similar to a pacemaker, was revealed in the interatrial septum (IAS) of the mammalian heart using histological methods. However, the electrical activity in this structure remains understudied. The aim of the present study was to examine the capability of the IAS to generate action potentials spontaneously and the effects of adrenergic stimulation on the bioelectrical activity of the IAS. For this purpose, we recorded the resting and action potentials in the multicellular isolated perfused preparations of the IAS and left atrium from the rat heart at the end of day 1 and at day 60 of postnatal life using the standard microelectrode technique. We found that α1-adrenomimetic phenylephrine (PE) modified the patterns of action potentials in the samples of IAS and the atrial myocardium from the animals of both ages. In the resting samples without any electrical stimulation, PE induced the generation of action potential in the IAS but not in the atrium because of oscillations in the level of cytoplasmic calcium. Application of the inhibitor of hyperpolarization activated current (If) ZD 7288 led to a decrease in the rate of slow diastolic depolarization of action potential in the IAS pacemaker cells, a decrease in the frequency, and the appearance of train activity. Thus, in newborn and adult rats, the IAS myocardium generates spontaneous electrical activity. A necessary condition for the occurrence of pacemaker activity is adrenergic stimulation. The capability to generate spontaneous activity is probably associated with the presence of pacemaker current If in the IAS cardiomyocytes.