DOCSLIB.ORG

Interactions Between Hippocampus and Medial Septum During Sharp Waves and Theta Oscillation in the Behaving Rat

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Interactions Between Hippocampus and Medial Septum During Sharp Waves and Theta Oscillation in the Behaving Rat The Journal of Neuroscience, July 15, 1999, 19(14):6191–6199 Interactions between Hippocampus and Medial Septum during Sharp Waves and Theta Oscillation in the Behaving Rat George Dragoi,1 Daniel Carpi,1 Michael Recce,2 Jozsef Csicsvari,1 and Gyo¨ rgy Buzsa´ki1 1Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102, and 2Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102 The medial septal region and the hippocampus are connected Because both SPW and the negative peak of local theta waves reciprocally via GABAergic neurons, but the physiological role correspond to the maximum discharge probability of CA1 py- of this loop is still not well understood. In an attempt to reveal ramidal cells and interneuron classes, the findings indicate that the physiological effects of the hippocamposeptal GABAergic the activity of medial septal neurons can be negatively (during projection, we cross-correlated hippocampal sharp wave SPW) or positively (during theta waves) correlated with the (SPW) ripples or theta activity and extracellular units recorded activity of hippocampal interneurons. We hypothesize that the in the medial septum and diagonal band of Broca (MSDB) in functional coupling between medial septal neurons and hip- freely moving rats. The majority of single MSDB cells (60%) pocampal interneurons varies in a state-dependent manner. were significantly suppressed during SPWs. Most cells inhib- ited during SPW (80%) fired rhythmically and phase-locked to Key words: EEG; GABAergic neurons; interneurons; ripples; the negative peak of the CA1 pyramidal layer theta waves. cholinergic system; lateral septum The septal region and the hippocampus are connected recipro- early formulation, neurons in the MSDB have been assumed to cally (Raisman, 1966). The two major components of the septo- play the role of a pacemaker by providing a coherent and rhyth- hippocampal projection consist of cholinergic and GABAergic mic drive to the hippocampus (Green and Arduini, 1954; Petsche cells (Shute and Lewis, 1963; Lewis et al., 1967; Ko¨hler et al., et al., 1962; Stumpf et al., 1962; Winson, 1978; Andersen et al., 1984), residing in the medial septum and the diagonal band of 1979). Subsequent studies have shown that MSDB GABAergic Broca (MSDB). The cholinergic projection terminates on all cells have the intrinsic propensity to oscillate at theta frequency types of hippocampal cells (Shute and Lewis, 1966; Frotscher and (Serafin et al., 1996) and suggested that a coordinated output of Leranth, 1985; Freund and Antal, 1988), whereas septal the GABAergic and cholinergic populations is responsible for GABAergic neurons specifically innervate GABAergic interneu- phase-locking hippocampal neurons (Stewart and Fox, 1989; Lee rons (Freund and Antal, 1988; Gulya´s et al., 1991). A subpopu- et al., 1994; Brazhnik and Fox, 1997). In contrast, other studies lation of the target GABAergic cells, in turn, projects back to the could not confirm the hypothesis that either the putative cholin- MSDB and preferentially innervates the GABAergic population ergic or GABAergic MSDB neurons discharge coherently during (Alonso and Ko¨hler, 1982; Gaykema et al., 1991; To´th et al., the theta cycle (Gaztelu and Bun˜o, 1982; Stewart and Fox, 1989, 1993). The hippocamposeptally projecting neurons contain the 1990; King et al., 1998). Two major technical problems have calcium binding protein calbindin (To´th and Freund, 1992; To´th hampered progress in this area of research. The first is the lack of et al., 1993). Hippocampal pyramidal cells project only to the unambiguous criteria for the identification of neuronal types from lateral septum (Alonso and Ko¨hler, 1982; Leranth and Frotscher, the extracellularly recorded spike patterns and the lack of histo- 1989). The main projection of the lateral septum is subcortical, logical identification of intracellularly studied neurons in acute and axon collaterals to the MSDB are either absent or very sparse experiments. The second problem is to isolate the contribution of (Gulya´s et al., 1991; Staiger and Nu¨rnberger, 1991; Leranth et al., the participating members in multiple loops (Vertes and Kocsis, 1992). Therefore, the major reciprocal communication between 1997). the septum and hippocampus is mediated by the MSDB and Theta rhythm is generated by a consortium of various pathways hippocampal GABAergic cells. The functional role of this recip- and mechanisms. In contrast, SPW bursts are known to emerge in rocal hippocamposeptal GABAergic loop is not understood. the recurrent collateral system of CA3 pyramidal cells (Buzsa´ki et The hippocampal formation displays two behaviorally and al., 1983). The synchronous discharge of pyramidal cells induces physiologically distinct patterns: theta waves and sharp waves high frequency and coherent discharge of the target interneurons, (SPWs). The importance of the septum in hippocampal theta including the calbindin-immunoreactive subclass, with axonal generation has been documented by numerous experiments. In an projection to the MSDB (To´th and Freund, 1992). We reasoned, therefore, that by studying the correlation between hippocampal Received March 8, 1999; revised May 3, 1999; accepted May 5, 1999. SPWs and MSDB neuronal activity, we can assess the unidirec- This work was supported by National Institutes of Health Grants NS34994 and MH54671. We thank Z. Borhegyi, H. Hirase, C. King, and Z. Nada´sdy for help and tional effect of hippocampal interneurons on MSDB neuronal support and T. F. Freund for his comments on this manuscript. populations. In addition, previous research has established that Correspondence should be addressed to Gyo¨rgy Buzsa´ki, Center for Molecular both pyramidal neurons and various classes of interneurons dis- and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, NJ 07102. play their highest discharge probability around the negative peak Copyright © 1999 Society for Neuroscience 0270-6474/99/196191-09$05.00/0 of theta waves in the CA1 pyramidal layer (Fox et al., 1986; 6192 J. Neurosci., July 15, 1999, 19(14):6191–6199 Dragoi et al. • Hippocamposeptal Inhibition Skaggs et al., 1996; Csicsvari et al., 1999). Using both SPWs and theta oscillations as reference signals for the maximum discharge probability of interneurons, we examined their impact on the activity of MSDB neurons in these two respective states. MATERIALS AND METHODS Animals and surgery. Ten adult male Sprague Dawley rats (weighting 300–500 gm) were anesthetized with a mixture (4 ml/kg) of ketamine (25 mg/ml), xylazine (1.3 mg/ml), and acepromazine (0.25 mg/ml) adminis- tered intramuscularly, following National Institutes of Health guidelines. Tungsten high-impedance electrodes (0.5–1 MV; Micro Probe Inc., MD) were mounted on movable drives and used to record the unit activity in the MSDB area. Each complete turn of the microdrive moved the electrode 0.3 mm axially. A hole (1 mm in diameter) was drilled above the septal area in the midline. After cutting the dura mater, the sagittal sinus was gently moved aside, and the tungsten electrode was lowered into the midline, ;1 mm above the medial septum [anteroposterior (AP), 0–0.7; lateral (L), 0; ventral (V), 5], according to the atlas coordinates of Paxinos and Watson (1997). In one rat, two such microdrives were used, one for recording from the MSDB and the other one from the lateral septum. The hippocampal recording electrodes were constructed from 50-mm-diameter stainless steel wire coated with insulation (California Fine Wire, Grover Beach, CA). Two of these wires, with 250 mm vertical Figure 1. Location of the recorded units in MSDB. Lines indicate elec- and 300 mm horizontal distance between their tips, were mounted on the trode tracks. Asterisks, Estimated location of recording sites. Image, same type of microdrive as in the high-impedance electrode. These ChAT immunostaining illustrating the recording track. Inset, Parvalbumin electrodes were unilaterally implanted through holes drilled above the immunostaining of an adjacent section; the arrow points to the midline. dorsal hippocampus (AP, 4; L, 2.5; V, 1.5). In addition, a pair of stainless Arrowheads mark the tracks of the same electrode on diagram and steel wires (100 mm in diameter) with 0.5 mm vertical tip separation was histological sections. Numbers represent distance (in millimeters) from placed in the fimbria (AP, 21.3; L, 1; V, 3.8) to stimulate the commis- bregma. aca, Anterior commissure; cc, corpus callosum; 2n, optic nerve. sural afferents to the CA1 region. The microdrives, as well as the Anatomical diagrams adapted from Paxinos and Watson (1997). stimulating electrodes, were fixed to the skull with dental acrylic. Two stainless steel screws driven into the bone above the cerebellum served as reference and ground electrodes. Two additional screws in the frontal reference events. Thus, the histograms reflect discharge probabilities. bone acted as anchors. After the operation, the rats were kept one to a The method for constructing phase histograms have been described cage, weighed, and inspected daily. Recording began after 1 week of previously (Csicsvari et al., 1999). In short, each spike was assigned to a recovery. given phase (bin size of 20°) of the normalized field cycle (ripple–theta). Recording and data analysis. The wire electrodes were lowered into the To reduce bin-border variability, the action potential times were substi- hippocampus until the CA1 pyramidal layer was identified. Positioning of tuted with a Gaussian kernel function. Histograms with mean bin value the hippocampal electrodes was aided by the response evoked by com- of less than five spikes were excluded from the analysis. Theta and ripple missural stimulation and by the presence of field ripples (200 Hz oscil- averages were obtained by averaging filtered signals, using the positive lations) associated with unit activity (Ylinen et al., 1995). After stable peaks of the ripples waves and the negative peaks of the theta cycle as the recording from the pyramidal cell layer, the tungsten electrode was zero reference. moved into the MSDB until discriminable septal units were recorded.
Load more

Recommended publications
  • Fos Activation of Selective Afferents to Ventral Tegmental Area During Cue-Induced Reinstatement of Cocaine Seeking in Rats
    The Journal of Neuroscience, September 19, 2012 • 32(38):13309–13325 • 13309 Behavioral/Systems/Cognitive Fos Activation of Selective Afferents to Ventral Tegmental Area during Cue-Induced Reinstatement of Cocaine Seeking in Rats Stephen V. Mahler and Gary S. Aston-Jones Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425 Ventral tegmental area (VTA) dopamine neurons are crucial for appetitive responses to Pavlovian cues, including cue-induced reinstate- ment of drug seeking. However, it is unknown which VTA inputs help activate these neurons, transducing stimuli into salient cues that drive drug-seeking behavior. Here we examined 56 VTA afferents from forebrain and midbrain that are Fos activated during cue-induced reinstatement. We injected the retrograde tracer cholera toxin ␤ subunit (CTb) unilaterally into rostral or caudal VTA of male rats. All animalsweretrainedtoself-administercocaine,thenextinguishedofthisbehavior.Onafinaltestday,animalswereexposedtoresponse- contingent cocaine-associated cues, extinction conditions, a non-cocaine-predictive CSϪ, or a novel environment, and brains were processed to visualize CTb and Fos immunoreactivity to identify VTA afferents activated in relation to behaviors. VTA-projecting neurons in subregions of medial accumbens shell, ventral pallidum, elements of extended amygdala, and lateral septum (but not pre- frontal cortex) were activated specifically during cue-induced cocaine seeking, and some of these were also activated proportionately to the degree of cocaine seeking. Surprisingly, though efferents from the lateral hypothalamic orexin field were also Fos activated during reinstatement, these were largely non-orexinergic. Also, VTA afferents from the rostromedial tegmental nucleus and lateral habenula were specifically activated during extinction and CSϪ tests, when cocaine was not expected.
    [Show full text]
  • Memory Loss from a Subcortical White Matter Infarct
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.51.6.866 on 1 June 1988. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry 1988;51:866-869 Short report Memory loss from a subcortical white matter infarct CAROL A KOOISTRA, KENNETH M HEILMAN From the Department ofNeurology, College ofMedicine, University ofFlorida, and the Research Service, Veterans Administration Medical Center, Gainesville, FL, USA SUMMARY Clinical disorders of memory are believed to occur from the dysfunction of either the mesial temporal lobe, the mesial thalamus, or the basal forebrain. Fibre tract damage at the level of the fornix has only inconsistently produced amnesia. A patient is reported who suffered a cerebro- vascular accident involving the posterior limb of the left internal capsule that resulted in a persistent and severe disorder of verbal memory. The inferior extent of the lesion effectively disconnected the mesial thalamus from the amygdala and the frontal cortex by disrupting the ventral amygdalofugal and thalamic-frontal pathways as they course through the diencephalon. This case demonstrates that an isolated lesion may cause memory loss without involvement of traditional structures associated with memory and may explain memory disturbances in other white matter disease such as multiple sclerosis and lacunar state. Protected by copyright. Memory loss is currently believed to reflect grey day of his illness the patient was transferred to Shands matter damage of either the mesial temporal lobe,' -4 Teaching Hospital at the University of Florida for further the mesial or the basal forebrain.'0 l evaluation. thalamus,5-9 Examination at that time showed the patient to be awake, Cerebrovascular accidents resulting in memory dys- alert, attentive and fully oriented.
    [Show full text]
  • The Neuromodulatory Basis of Emotion
    1 The Neuromodulatory Basis of Emotion Jean-Marc Fellous Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California The Neuroscientist 5(5):283-294,1999. The neural basis of emotion can be found in both the neural computation and the neuromodulation of the neural substrate mediating behavior. I review the experimental evidence showing the involvement of the hypothalamus, the amygdala and the prefrontal cortex in emotion. For each of these structures, I show the important role of various neuromodulatory systems in mediating emotional behavior. Generalizing, I suggest that behavioral complexity is partly due to the diversity and intensity of neuromodulation and hence depends on emotional contexts. Rooting the emotional state in neuromodulatory phenomena allows for its quantitative and scientific study and possibly its characterization. Key Words: Neuromodulation, Emotion, Affect, Hypothalamus, Amygdala, Prefrontal the behavior1 that this substrate mediates. The Introduction neuromodulation of 'cognitive centers' results in phenomena pertaining to emotional influences of The scientific study of the neural basis of cognitive processing. Neuromodulations of memory emotion is an active field of experimental and structures explain the influence of emotion on theoretical research (See (1,2) for reviews). Partly learning and recall; the neuromodulation of specific because of a lack of a clear definition (should it reflex pathways explains the influence of the exists) of what emotion is, and probably because of emotional state on elementary motor behaviors, and its complexity, it has been difficult to offer a so forth... neuroscience framework in which the influence of The instantaneous pattern of such modulations emotion on behavior can be studied in a (i.e.
    [Show full text]
  • Thalamus and Limbic System Important Doctors Notes Notes/Extra Explanation Please View Our Editing File Before Studying This Lecture to Check for Any Changes
    Color Code Thalamus and Limbic System Important Doctors Notes Notes/Extra explanation Please view our Editing File before studying this lecture to check for any changes. Objectives At the end of the lecture, the students should be able to: ✓ Describe the anatomy and main functions of the thalamus. ✓ Name and identify different nuclei of the thalamus. ✓ Describe the main connections and functions of thalamic nuclei. ✓ Name and identify different parts of the limbic system. ✓ Describe main functions of the limbic system. ✓ Describe the effects of lesions of the limbic system. Thalamus 02:04 o It is the largest nuclear mass of the whole body. o It is the largest part of the diencephalon o It is formed of: two oval masses of grey matter. o It is the gateway to the cortex.(the last station for sensory fibers before it project to the cortex) o Resemble a small hen. o Together with the hypothalamus they form the lateral wall of the 3rd ventricle. o The thalamus sends received information to the cerebral cortex from different brain regions. o Axons from every sensory system (except olfaction) synapse in the thalamus as the last relay site 'last pit stop' before the information reaches the cerebral cortex. o There are some thalamic nuclei that receive input from: 1. Cerebellar nuclei, 2. Basal ganglia 3. Limbic-related brain regions. Thalamus Relations Relation = surfaces S L T 3 It has 4 surfaces & 2 ends. I Surfaces: Superior: (S) Inferior: (I) Lateral ventricle and fornix. Hypothalamus, anteriorly & Ends: Subthalamus posteriorly. Anterior end: Medial: (3) Lateral:(L) Forms a projection, called the anterior tubercle.
    [Show full text]
  • White Matter Anatomy: What the Radiologist Needs to Know
    White Matter Anatomy What the Radiologist Needs to Know Victor Wycoco, MBBS, FRANZCRa, Manohar Shroff, MD, DABR, FRCPCa,*, Sniya Sudhakar, MBBS, DNB, MDb, Wayne Lee, MSca KEYWORDS Diffusion tensor imaging (DTI) White matter tracts Projection fibers Association Fibers Commissural fibers KEY POINTS Diffusion tensor imaging (DTI) has emerged as an excellent tool for in vivo demonstration of white matter microstructure and has revolutionized our understanding of the same. Information on normal connectivity and relations of different white matter networks and their role in different disease conditions is still evolving. Evidence is mounting on causal relations of abnormal white matter microstructure and connectivity in a wide range of pediatric neurocognitive and white matter diseases. Hence there is a pressing need for every neuroradiologist to acquire a strong basic knowledge of white matter anatomy and to make an effort to apply this knowledge in routine reporting. INTRODUCTION (Fig. 1). However, the use of specific DTI sequences provides far more detailed and clini- DTI has allowed in vivo demonstration of axonal cally useful information. architecture and connectivity. This technique has set the stage for numerous studies on normal and abnormal connectivity and their role in devel- DIFFUSION TENSOR IMAGING: THE BASICS opmental and acquired disorders. Referencing established white matter anatomy, DTI atlases, Using appropriate magnetic field gradients, and neuroanatomical descriptions, this article diffusion-weighted sequences can be used to summarizes the major white matter anatomy and detect the motion of the water molecules to and related structures relevant to the clinical neurora- from cells. This free movement of the water mole- diologist in daily practice.
    [Show full text]
  • The Effect of Lesions in the Septal Region on Muricide, Irritability, and Activity in the Long-Evans Rat
    Physiological Psychology 1978, Vol. 6 (1), 36-42 The effect of lesions in the septal region on muricide, irritability, and activity in the Long-Evans rat TAYLOR WALLACE and B. MICHAEL THORNE Mississippi State University, Mississippi State, Mississippi 39762 The present research was designed to examine the effects upon mouse killing of different types of damage in and around the septal area. The three types of septal damage incurred were: damage restricted to the septum (SS), damage ventral to the septum (VS), and damage to both the septum and ventrally located structures (LS). Irritability and activity (both horizon­ tal and vertical) were also assessed. The results showed that damage restricted to the septum had no effect on muricide. Extensive damage to the septal region was necessary to increase the probability of mouse killing. All brain-damaged groups were significantly more irritable than the operated controls, with Group VS being the most irritable. Furthermore, killers were found to be significantly more irritable than nonkillers. Group LS animals were the least active of any group on both horizontal and vertical activity assessments. All brain­ damaged groups were significantly less active than controls in regard to rearing. A variety of manipulations has been found to in­ by Latham and Thorne (1974), in which rats of the crease the probability of the mouse-killing response strain tested by Malick showed an increase in killing in nonkillers, including food deprivation (Malick, after septal damage, while no change was seen in 1975; Rager & Thorne, 1977), the strain of rat used animals of the strain used by Miczek and Grossman.
    [Show full text]
  • Forebrain Origins and Terminations of the Medial Forebrain Bundle Metabolically Activated by Rewarding Stimulation Or by Reward- Blocking Doses of Pimozide’
    0270.6474/85/0505-1246$02.00/O The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 5, No. 5, pp. 1246-1261 Printed in U.S.A. May 1985 Forebrain Origins and Terminations of the Medial Forebrain Bundle Metabolically Activated by Rewarding Stimulation or by Reward- blocking Doses of Pimozide’ C. R. GALLISTEL,* Y. GOMITA,3 ELNA YADIN,4 AND KENNETH A. CAMPBELL5 Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Abstract iological investigation as a likely substrate for the rewarding effect of MFB stimulation. They also suggest that dopami- Using [14C]-2-deoxyglucose autoradiography, we deter- nergic projection systems may not form part of the reward mined which forebrain and diencephalic areas showed met- pathway itself. abolic alterations in response to unilateral electrical stimu- lation of the posterior medial forebrain bundle at parameters Behavioral experiments, using methods for determining quantita- chosen to produce a just-submaximal rewarding effect. At tive properties of the neural substrate, have led to the conclusion these parameters, only a few areas were activated. There that the directly stimulated substrate for electrical self-stimulation of was no detectable activation anterior or dorsal to the genu the medial forebrain bundle (MFB) is comprised in substantial part of the corpus callosum. Just anterior to the anterior commis- of long, thin myelinated axons descending from forebrain nuclei to sure, there was strong activation of the vertical limb of the the anterior ventral tegmentum (C. Bielajew and P. Shizgal, manu- diagonal band of Broca, with a focus in the nucleus of the script submitted for publication; Gallistel et al., 1981).
    [Show full text]
  • Module 3. the Blood Supply of the Brain Relating Vascular and Functional Anatomy
    Module 3. The Blood Supply of the Brain Relating Vascular and Functional Anatomy Objectives for Module 3 Knowledge § Describe or sketch the course of the major arteries and their branches that comprise the carotid and vertebral-basilar systems. § Name the major arteries or branches whose territories include the following structures: Ø Lateral parts of the hemisphere and large regions of internal capsule and basal ganglia (deep structures) Ø Anterior Medial and Superior parts of hemisphere including anterior corpus callosum Ø Posterior Medial and Inferior parts of the hemisphere including posterior corpus callosum Ø Thalamus Ø Medial brainstem Ø Lateral brainstem and Cerebellum § Name the major arteries (and branches) that supply: Primary motor cortex for face, arm, leg; and corticobulbar and corticospinal fibers in deep white matter of hemisphere, and throughout the rest of their course in the forebrain and brainstem. § Name the major arteries that supply the different components of the visual system, regions involved in language processing/production, spatial attention and visual-spatial orientation. § List 4 important regions where collateral circulation may provide alternate routes for blood flow to the brain. Clinical Applications and Reasoning § Explain why collateral circulation may not protect against brain ischemia when a major artery is abruptly occluded. § Explain why a slowly developing occlusion of the internal carotid artery in the neck might be totally asymptomatic. § Name at least 3 structures where both intraparenchymal hemorrhages and small-vessel (lacunar) infarcts are common, and suggest an anatomic feature shared by their blood vessels. It may be helpful to look at the relevant StrokeSTOP reference drawings as you read this module The brain derives its arterial supply from the paired carotid and vertebral arteries.
    [Show full text]
  • Limbic System
    Limbic System Objective • To learn the complex 3-dimensional anatomy of some of the C-shaped deep brain structures • To become familiar with the brain systems for emotions and learning and memory, with an emphasis on the amygdala and hippocampal formation NTA Ch 15, pgs. 447-462 Key Figs. 15-1 through 15-6 Table 15-1 Clinical Case #13 Temporal lobe epilepsy; CC13-1 Self evaluation • Be able to identify all structures listed in key terms and describe briefly their principal functions • Use neuroanatomy on the web to test your understanding I-1 General anatomical organization of the limbic system The medial surfaces of the telencephalon and diencephalon are illustrated in the top panel. Below is a “cut-away” view of diencephalic and telencephalic nuclei and tracts. Use these two illustrations to familiarize yourself with the key structures of the limbic system. On the medial brain surface, identify the limbic association areas: the cingulate and parahippocampal gyri and the cortex of the temporal pole. The orbital gyri are not visible on this slide. What are some functions of the parahippocampal gyrus and temporal pole? The amygdala and rostral hippocampal formation are under the region of the uncus. Space occupying lesions above the cerebellar tentorium may cause the uncus on the side of the lesion to become displaced medially thereby squeezing the midbrain and the third nerves. This is termed uncal herniation. The more caudal portions of the hippocampal formation are located beneath the parahippocampal gyrus. The septal nuclei (see outline of approximate boundaries in the lower brain view) are located on the lateral surface of the septum pellucidum.
    [Show full text]
  • Role of Brain Angiotensin AT1 Receptor in the Carbachol- Induced Natriuresis and Expression of Nnos in the Locus Coeruleus and Proximal Convoluted Tubule
    Physiol. Res. 56: 383-391, 2007 Role of Brain Angiotensin AT1 Receptor in the Carbachol- Induced Natriuresis and Expression of nNOS in the Locus Coeruleus and Proximal Convoluted Tubule M. WANG, C.L. JIANG, C.Y. WANG, Q.Y. YAO Department of Physiology, Dalian Medical University, Dalian, China Received April 4, 2006 Accepted July 10, 2006 On-line available August 22, 2006 Summary Central administration of losartan effectively blocked the increase of blood pressure and drinking response induced by angiotensin II (Ang II) or carbachol. However, the relationship between angiotensin AT1 receptors and the natriuresis induced by brain cholinergic stimuli is still not clear. The purpose of the study is to reveal the role of brain angiotensin AT1 receptor in the carbachol-induced natriuresis and expression of neuronal nitric oxide synthase (nNOS) in the locus coeruleus (LC) and proximal convoluted tubule (PCT). Our results indicated that 40 min after intracerebroventricular (ICV) injection of carbachol (0.5 μg), urinary sodium excretion was significantly increased to 0.548±0.049 μmol·min-1·100 g-1. Immunohistochemistry showed that carbachol induced an increase of neuronal nitric oxide synthase immunoreactivity (nNOS-IR) in the LC and renal proximal tubular cells. After pretreatment with losartan (20 μg), carbachol-induced urinary sodium excretion was reduced to 0.249±0.067 μmol·min-1·100 g-1. The same was true for carbachol-induced increase of nNOS-IR in the LC and PCT. The present data suggest that ICV cholinergic stimulation could induce a natriuresis and upregulate the activity of nNOS in the LC and PCT.
    [Show full text]
  • Clinically Indicated Electrical Stimulation Strategies to Treat
    SUPPLEMENT ARTICLE Clinically indicated electrical stimulation strategies to treat patients with medically refractory epilepsy †1Ali Izadi, †‡1Katelynn Ondek, †Amber Schedlbauer, †§Inna Keselman, †‡Kiarash Shahlaie, and †‡*Gene Gurkoff Epilepsia Open, 3(s2):198–209, 2018 doi: 10.1002/epi4.12276 SUMMARY Focal epilepsies represent approximately half of all diagnoses, and more than one-third of these patients are refractory to pharmacologic treatment. Although resection can result in seizure freedom, many patients do not meet surgical criteria, as seizures may be multifocal in origin or have a focus in an eloquent region of the brain. For these indi- viduals, several U.S. Food and Drug Administration (FDA)–approved electrical stimu- lation paradigms serve as alternative options, including vagus nerve stimulation, responsive neurostimulation, and stimulation of the anterior nucleus of the thalamus. All of these are safe, flexible, and lead to progressive seizure control over time when used as an adjunctive therapy to antiepileptic drugs. Focal epilepsies frequently involve significant comorbidities such as cognitive decline. Similar to antiepilepsy medications and surgical resection, current stimulation targets and parameters have yet to address cognitive impairments directly, with patients reporting persistent comorbidities asso- ciated with focal epilepsy despite a significant reduction in the number of their sei- zures. Although low-frequency theta oscillations of the septohippocampal network Ali Izadi has a PhD in are critical for modulating cellular activity and, in turn, cognitive processing, the coor- neuroscience and is dination of neural excitability is also imperative for preventing seizures. In this review, focused on applying we summarize current FDA-approved electrical stimulation paradigms and propose novel DBS paradigms that theta oscillations of the medial septal nucleus represent a novel neuromodulation to treat neurologic target for concurrent seizure reduction and cognitive improvement in epilepsy.
    [Show full text]
  • Olfactory Pathways and Limbic System
    903 Olfactory and Limbic OLFACTORY PATHWAYS AND LIMBIC SYSTEM I. OLFACTORY PATHWAYS The sense of smell is much less essential than vision, audition or the somatic senses, and will therefore receive less emphasis in this course. However, since olfactory dysfunction can be an important diagnostic sign, it is important to have at least a rudimentary knowledge of the olfactory pathways. Olfactory Receptors. The olfactory receptors (Fig. 1) are embedded in a specialized patch of yellow-tinted mucous membrane in the roof of the nasal cavity. These receptors are bipolar neurons covered with modified, non-motile cilia. These cilia probably contain the active sites for the olfactory transduction process. Axons from the olfactory receptors enter small nerve bundles (collectively termed the 1st cranial nerve) which pass through the perforations in the cribiform plate of the ethmoid bone and promptly enter the olfactory bulb. These nerve bundles can be severed as a result of skull fractures or other pathology in this region with a resulting partial or complete anosmia (loss of sense of smell). Much of the sensation we consider to be taste is actually olfactory so patients with anosmia often complain bitterly about loss of pleasure from eating. Olfactory Bulb. The olfactory bulbs lie on the ventral aspect of the frontal lobes. The olfactory bulbs and all other parts of the olfactory pathways are telencephalic derivatives. Within the olfactory bulbs the olfactory nerves synapse on mitral cells whose axons project directly to the olfactory cortex. Olfactory Tract. The olfactory tract connects the olfactory bulb with the cerebral hemispheres. Axons of mitral cells pass directly back to the olfactory cortex on the ipsilateral side (Fig.
    [Show full text]