DOCSLIB.ORG

View Full Page

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
View Full Page The Journal of Neuroscience, August 15, 1999, 19(16):7230–7237 Rat Hippocampal Neurons Are Critically Involved in Physiological Improvement of Memory Processes Induced by Cholecystokinin-B Receptor Stimulation Ange´ lique Sebret,1 Isabelle Le´ na,1 Dominique Cre´te´,1 Toshimitsu Matsui,2 Bernard P. Roques,1 and Vale´ rie Dauge´ 1 1De´ partement de Pharmacochimie Mole´ culaire et Structurale, Institut National de la Sante´ et de la Recherche Me´ dicale U266, Centre National de la Recherche Scientifique, Unite´ Mixte de Recherche 8600, Unite´ de Formation et de Recherche des Sciences Pharmaceutiques et Biologiques, 75270 Paris Cedex 06, France, and 2Third Division Department of Medicine, Kobe University School of Medicine, Kobe 650–0017 Japan The involvement in memory processes of the neuropeptide the controls (2 hr time interval) when it was injected before the cholecystokinin (CCK) through its interaction with the CCK-B acquisition or the retrieval phase of the task. In addition, an receptors was studied. The two-trial recognition memory task increase of the extracellular levels of CCK-like immunoreactivity was used. Control animals showed recognition memory after a in the hippocampus of rats during the acquisition and retention 2 hr time interval but not aftera6hrtime interval between the phase of the task was observed. Finally, CCK-B receptor- two trials. The improving effect of a selective CCK-B agonist, deficient mice have an impairment of performance in the mem- BC 264, intraperitoneally administered (0.3 mg/kg) in the re- ory task (2 hr time interval). trieval phase of the task (6 hr time interval), was also observed Together, these results support the physiological involvement after its injection (1 pmol/0.5 ml) in the dorsal subiculum/CA1 of of the CCKergic system through its interaction with CCK-B the hippocampus but not in the caudate/putamen nucleus or in receptors in the hippocampus to improve performance of ro- the prefrontal cortex of rats. The CCK-B antagonist L-365,260 dents in the spatial recognition memory test. injected (10 ng/0.5 ml) into this region of the hippocampus abolished the improving effect of BC 264 injected intraperito- Key words: cholecystokinin-B receptors; spatial memory; neally. Furthermore, L-365,260 injected in the hippocampus CA1; prelimbic-infralimbic cortex; CCK release; CCK-B suppressed the recognition of the novel arm normally found in receptor-deficient mice The sulfated octapeptide cholecystokinin (CCK8 ) exerts its ef- Taghzouti et al., 1999). These effects were dependent on the fects through two G-protein-coupled receptors (Wank et al., dopaminergic (DAergic) system in the anterior part of the nu- 1992; Lee et al., 1993): CCK-B receptors are found essentially in cleus accumbens (N.Acc.) (Ladurelle et al., 1997). the CNS and CCK-A receptors are highly concentrated in the However, the systemic effects of BC 264 could not result from gastrointestinal tract but are also found in particular brain struc- a direct interaction between CCK-B receptors and DAergic ter- tures (Hill et al., 1987; Mercer and Beart, 1997). minals in the N.Acc., because opposite behavioral and biochem- Modulation of memory processes by the CCKergic system has ical responses were observed when this compound was locally been demonstrated in studies using, in most of them, active and injected in the anterior N.Acc. (Dauge´ et al., 1992; Ladurelle et passive avoidance tests (Katsuura and Itoh, 1986; for review, see al., 1993). This means that stimulation of CCK-B receptors local- Itoh and Lal, 1990; Dauge´ and Le´na, 1998). However, the role of ized in cerebral structures other than the N.Acc. could be respon- each receptor type and the physiological involvement of the sible of the effects occurring at this level. The neurons of the CCKergic system in memory processes remain poorly under- N.Acc. receive an intense DAergic innervation from the ventral stood. We have shown recently that systemic administration of tegmental area and glutamatergic projections from the hippocam- selective CCK-B agonists, such as BC 264 (Charpentier et al., pus, the prefrontal cortex, and the amygdala (Groenewegen et al., 1988), pBC 264 (Corringer et al., 1992), or RB400 (Million et al., 1991). Interestingly, anatomical data showed that CCKergic ter- 1997), improved the cognitive performances of rats measured in minals establish direct synaptic contact with glutamatergic neu- the spontaneous alternation test and a spatial two-trial memory rons of the hippocampus that project to the N.Acc. (Totterdell and task (Ladurelle et al., 1997; Million et al., 1997; Le´na et al., 1999; Smith, 1986), and BC 264 was shown to increase the glutamate and aspartate release and the firing rate of the CA1 neurons of the Received March 23, 1999; revised May 17, 1999; accepted May 20, 1999. hippocampus of rats (Dauge´ et al., 1990; Migaud et al., 1994). We thank H. Dhoˆtel for the synthesis of BC 264 and M. Beinfeld for a critical The present study was therefore designed to define the role of reading of this manuscript. brain structures, in particular the hippocampus and the prefrontal Correspondence should be addressed to Dr. Vale´rie Dauge´, De´partement de Pharmacochimie Mole´culaire et Structurale, Institut National de la Sante´etdela cortex, in the effects of BC 264 in a two-trial memory task in rats. Recherche Me´dicale U266, Centre National de la Recherche Scientifique, Unite´ This was achieved by local injection of BC 264 or the selective Mixte de Recherche 8600, Unite´ de Formation et de Recherche des Sciences Pharmaceutiques et Biologiques, 4, avenue de l’Observatoire, 75270 Paris Cedex 06, CCK-B antagonist L-365,260 (Chang and Lotti, 1986) in these France. structures. Furthermore, the physiological involvement of the Copyright © 1999 Society for Neuroscience 0270-6474/99/197230-08$05.00/0 CCKergic system in a spatial memory task was investigated using Sebret et al. • CCK-B Receptor Activation Improved Spatial Memory J. Neurosci., August 15, 1999, 19(16):7230–7237 7231 local injection of L-365,260 in the hippocampus of rats, by behav- beginning of each trial, but the position of the closed arm was alternated ioral analysis of mice with a deletion of CCK-B receptors (Nagata to the left or to the right of this arm, respectively, for half of the animals of each group tested. et al., 1996) and by quantification of the extracellular levels of In some local injection experiments with rats, the first and second CCK-like immunoreactivity (CCK-LIR) in the hippocampus by trials, which lasted 3 and 2 min, respectively, were separated bya6hr microdialysis in rat submitted or not to the memory task. time interval for which the control rats did not recognize the novel arm and explored the three arms equally (33.3% of visit duration in each arm). The time interval of 6 hr allowed the memory-improving effect of MATERIALS AND METHODS the drug to be studied, assessed by an increase in the exploration of the novel arm. Subjects In the other experiments, the trials were separated bya2hrtime Male Wistar rats (Charles River, Saint-Aubin les Elbeuf, France) weigh- interval for which the control rats spent more time exploring the novel ing 180–200 gm at the time of surgery were used. They were housed in arm. This time interval allowed the memory-impairment effect of the groups of four in a temperature-controlled (22 6 1°C) and humidity- drug to be studied. controlled (50 6 5%) environment and had access to food and water ad For microdialysis experiments, the two trials lasted 30 min because the libitum. Each animal was handled daily for 3 d before the experiments. samples were collected every 30 min. During the intertrial interval, rats CCK-B/gastrin receptor-deficient mice were provided from the origi- were put back in the microdialysis box. The trials were separated by a 2 nal background 129sv/C57BL6 mice (Nagata et al., 1996). Breeding and hr time interval. This time interval allowed changes in levels of CCK- genotype analysis have been done by Transgenic Alliance (L’Arbresle, LIR to be linked to the cognitive process. France). Twenty-five CCK-B receptor-deficient mice (13 males and 12 For mutant and wild-type mice, the task is the same as the previously females) and 26 mice (13 males and 13 females) of 129sv/C57BL6 genetic described one for the rats. The first and second trials, which lasted 3 and background (3 months old) were used. They were housed at least 1 week 2 min, respectively, were separated bya2hrtimeinterval for which before the experiments in the laboratory in a temperature-controlled control mice recognized and spent more time in the novel arm. (22 6 1°C) and humidity-controlled (50 6 5%) environment and had access to food and water ad libitum. The animals were treated as approved by the local committee and in Experimental procedure for local injections in the two-trial accordance with the NIH Guidelines for the Care and Use of Laboratory memory task in rats Animals (1985). Dorsal subiculum/CA1 of the hippocampus. In the dorsal subiculum/CA1 of the hippocampus, four series of experiments were done. Surgery The first consisted of a local injection of the CCK-B antagonist Rats were anesthetized by an intraperitoneal injection of chloral hydrate L-365,260 15 min after the intraperitoneal injection of the CCK-B (400 mg/kg), mounted in a stereotaxic apparatus (Unime´canique), and agonist BC 264. The agonist was administered 30 min before the second implanted bilaterally with 25-gauge stainless steel cannula guides (0.6 trial (i.e., the retrieval phase) aftera6hrintertrial interval. The follow- mm in external diameter) for local injection experiments.
Load more

Recommended publications
  • Glutamate Binding in Primate Brain
    Journal of Neuroscience Research 27512-521 (1990) Quisqualate- and NMDA-Sensitive [3H]Glutamate Binding in Primate Brain A.B. Young, G.W. Dauth, Z. Hollingsworth, J.B. Penney, K. Kaatz, and S. Gilman Department of Neurology. University of Michigan, Ann Arbor Excitatory amino acids (EAA) such as glutamate and Young and Fagg, 1990). Because EAA are involved in aspartate are probably the neurotransmitters of a general cellular metabolic functions, they were not orig- majority of mammalian neurons. Only a few previous inally considered to be likcl y neurotransmitter candi- studies have been concerned with the distribution of dates. Electrophysiological studies demonstrated con- the subtypes of EAA receptor binding in the primate vincingly the potency of these substances as depolarizing brain. We examined NMDA- and quisqualate-sensi- agents and eventually discerned specific subtypes of tive [3H]glutamate binding using quantitative autora- EAA receptors that responded preferentially to EAA an- diography in monkey brain (Macaca fascicularis). alogs (Dingledine et al., 1988). Coincident with the elec- The two types of binding were differentially distrib- trophysiological studies, biochemical studies indicated uted. NMDA-sensitive binding was most dense in that EAA were released from slice and synaptosome dentate gyrus of hippocampus, stratum pyramidale preparations in a calcium-dependent fashion and were of hippocampus, and outer layers of cerebral cortex. accumulated in synaptosomc preparations by a high-af- Quisqualate-sensitive binding was most dense in den- finity transport system. With these methodologies, EAA tate gyrus of hippocampus, inner and outer layers of release and uptake were found to be selectively de- cerebral cortex, and molecular layer of cerebellum.
    [Show full text]
  • Gene Expression of Prohormone and Proprotein Convertases in the Rat CNS: a Comparative in Situ Hybridization Analysis
    The Journal of Neuroscience, March 1993. 73(3): 1258-1279 Gene Expression of Prohormone and Proprotein Convertases in the Rat CNS: A Comparative in situ Hybridization Analysis Martin K.-H. Schafer,i-a Robert Day,* William E. Cullinan,’ Michel Chri?tien,3 Nabil G. Seidah,* and Stanley J. Watson’ ‘Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0720 and J. A. DeSeve Laboratory of *Biochemical and 3Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W lR7 Posttranslational processing of proproteins and prohor- The participation of neuropeptides in the modulation of a va- mones is an essential step in the formation of bioactive riety of CNS functions is well established. Many neuropeptides peptides, which is of particular importance in the nervous are synthesized as inactive precursor proteins, which undergo system. Following a long search for the enzymes responsible an enzymatic cascade of posttranslational processing and mod- for protein precursor cleavage, a family of Kexin/subtilisin- ification events during their intracellular transport before the like convertases known as PCl, PC2, and furin have recently final bioactive products are secreted and act at either pre- or been characterized in mammalian species. Their presence postsynaptic receptors. Initial endoproteolytic cleavage occurs in endocrine and neuroendocrine tissues has been dem- C-terminal to pairs of basic amino acids such as lysine-arginine onstrated. This study examines the mRNA distribution of (Docherty and Steiner, 1982) and is followed by the removal these convertases in the rat CNS and compares their ex- of the basic residues by exopeptidases. Further modifications pression with the previously characterized processing en- can occur in the form of N-terminal acetylation or C-terminal zymes carboxypeptidase E (CPE) and peptidylglycine a-am- amidation, which is essential for the bioactivity of many neu- idating monooxygenase (PAM) using in situ hybridization ropeptides.
    [Show full text]
  • Distinct Transcriptomic Cell Types and Neural Circuits of the Subiculum and Prosubiculum Along 2 the Dorsal-Ventral Axis 3 4 Song-Lin Ding1,2,*, Zizhen Yao1, Karla E
    bioRxiv preprint doi: https://doi.org/10.1101/2019.12.14.876516; this version posted December 15, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Distinct transcriptomic cell types and neural circuits of the subiculum and prosubiculum along 2 the dorsal-ventral axis 3 4 Song-Lin Ding1,2,*, Zizhen Yao1, Karla E. Hirokawa1, Thuc Nghi Nguyen1, Lucas T. Graybuck1, Olivia 5 Fong1, Phillip Bohn1, Kiet Ngo1, Kimberly A. Smith1, Christof Koch1, John W. Phillips1, Ed S. Lein1, 6 Julie A. Harris1, Bosiljka Tasic1, Hongkui Zeng1 7 8 1Allen Institute for Brain Science, Seattle, WA 98109, USA 9 10 2Lead Contact 11 12 *Correspondence: [email protected] (SLD) 13 14 15 Highlights 16 17 1. 27 transcriptomic cell types identified in and spatially registered to “subicular” regions. 18 2. Anatomic borders of “subicular” regions reliably determined along dorsal-ventral axis. 19 3. Distinct cell types and circuits of full-length subiculum (Sub) and prosubiculum (PS). 20 4. Brain-wide cell-type specific projections of Sub and PS revealed with specific Cre-lines. 21 22 23 In Brief 24 25 Ding et al. show that mouse subiculum and prosubiculum are two distinct regions with differential 26 transcriptomic cell types, subtypes, neural circuits and functional correlation. The former has obvious 27 topographic projections to its main targets while the latter exhibits widespread projections to many 28 subcortical regions associated with reward, emotion, stress and motivation.
    [Show full text]
  • Hippocampal Subfield Volumes Are Uniquely Affected in PTSD and Depression
    bioRxiv preprint doi: https://doi.org/10.1101/739094; this version posted August 21, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Hippocampal subfields in PTSD and depression Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group Lauren E. Salminen1, Philipp G. Sämann2, Yuanchao Zheng3, Emily L. Dennis1,4–6, Emily K. Clarke-Rubright7,8, Neda Jahanshad1, Juan E. Iglesias9–11, Christopher D. Whelan12,13, Steven E. Bruce14, Jasmeet P. Hayes15, Soraya Seedat16, Christopher L. Averill17, Lee A. Baugh18–20, Jessica Bomyea21,22, Joanna Bright1, Chanellé J. Buckle16, Kyle Choi23,24, Nicholas D. Davenport25,26, Richard J. Davidson27–29, Maria Densmore30,31, Seth G. Disner25,26, Stefan du Plessis16, Jeremy A. Elman22,32, Negar Fani33, Gina L. Forster18,19,34, Carol E. Franz22,32, Jessie L. Frijling35, Atilla Gonenc36–38, Staci A. Gruber36–38, Daniel W. Grupe27, Jeffrey P. Guenette39, Courtney C. Haswell7,8, David Hofmann40, Michael Hollifield41, Babok Hosseini42, Anna R. Hudson43, Jonathan Ipser44, Tanja Jovanovic45, Amy Kennedy-Krage42, Mitzy Kennis46,47, Anthony King48, Philipp Kinzel49, Saskia B. J. Koch35,50, Inga Koerte4, Sheri M. Koopowitz44, Mayuresh S. Korgaonkar51, William S. Kremen21,22,32, John Krystal17,52, Lauren A. M. Lebois37,53, Ifat Levy17,54, Michael J. Lyons55, Vincent A. Magnotta56, Antje Manthey57, Soichiro Nakahara58,59, Laura Nawijn35,60, Richard W. J.
    [Show full text]
  • Rhesus Monkey Brain Atlas Subcortical Gray Structures
    Rhesus Monkey Brain Atlas: Subcortical Gray Structures Manual Tracing for Hippocampus, Amygdala, Caudate, and Putamen Overview of Tracing Guidelines A) Tracing is done in a combination of the three orthogonal planes, as specified in the detailed methods that follow. B) Each region of interest was originally defined in the right hemisphere. The labels were then reflected onto the left hemisphere and all borders checked and adjusted manually when necessary. C) For the initial parcellation, the user used the “paint over function” of IRIS/SNAP on the T1 template of the atlas. I. Hippocampus Major Boundaries Superior boundary is the lateral ventricle/temporal horn in the majority of slices. At its most lateral extent (subiculum) the superior boundary is white matter. The inferior boundary is white matter. The anterior boundary is the lateral ventricle/temporal horn and the amygdala; the posterior boundary is lateral ventricle or white matter. The medial boundary is CSF at the center of the brain in all but the most posterior slices (where the medial boundary is white matter). The lateral boundary is white matter. The hippocampal trace includes dentate gyrus, the CA3 through CA1 regions of the hippocamopus, subiculum, parasubiculum, and presubiculum. Tracing A) Tracing is done primarily in the sagittal plane, working lateral to medial a. Locate the most lateral extent of the subiculum, which is bounded on all sides by white matter, and trace. b. As you page medially, tracing the hippocampus in each slice, the superior, anterior, and posterior boundaries of the hippocampus become the lateral ventricle/temporal horn. c. Even further medially, the anterior boundary becomes amygdala and the posterior boundary white matter.
    [Show full text]
  • Slicer 3 Tutorial the SPL-PNL Brain Atlas
    Slicer 3 Tutorial The SPL-PNL Brain Atlas Ion-Florin Talos, M.D. Surgical Planning Laboratory Brigham and Women’s Hospital -1- http://www.slicer.org Acknowledgments NIH P41RR013218 (Neuroimage Analysis Center) NIH U54EB005149 (NA-MIC) Surgical Planning Laboratory Brigham and Women’s Hospital -2- http://www.slicer.org Disclaimer It is the responsibility of the user of 3DSlicer to comply with both the terms of the license and with the applicable laws, regulations and rules. Surgical Planning Laboratory Brigham and Women’s Hospital -3- http://www.slicer.org Material • Slicer 3 http://www.slicer.org/pages/Special:Slicer_Downloads/Release Atlas data set http://wiki.na-mic.org/Wiki/index.php/Slicer:Workshops:User_Training_101 • MRI • Labels • 3D-models Surgical Planning Laboratory Brigham and Women’s Hospital -4- http://www.slicer.org Learning Objectives • Loading the atlas data • Creating and displaying customized 3D-views of neuroanatomy Surgical Planning Laboratory Brigham and Women’s Hospital -5- http://www.slicer.org Prerequisites • Slicer Training Slicer 3 Training 1: Loading and Viewing Data http://www.na-mic.org/Wiki/index.php/Slicer:Workshops:User_Training_101 Surgical Planning Laboratory Brigham and Women’s Hospital -6- http://www.slicer.org Overview • Part 1: Loading the Brain Atlas Data • Part 2: Creating and Displaying Customized 3D views of neuroanatomy Surgical Planning Laboratory Brigham and Women’s Hospital -7- http://www.slicer.org Loading the Brain Atlas Data Slicer can load: • Anatomic grayscale data (CT, MRI) ……… ………………………………….
    [Show full text]
  • Amygdala Functional Connectivity, HPA Axis Genetic Variation, and Life Stress in Children and Relations to Anxiety and Emotion Regulation
    Journal of Abnormal Psychology © 2015 American Psychological Association 2015, Vol. 124, No. 4, 817–833 0021-843X/15/$12.00 http://dx.doi.org/10.1037/abn0000094 Amygdala Functional Connectivity, HPA Axis Genetic Variation, and Life Stress in Children and Relations to Anxiety and Emotion Regulation David Pagliaccio, Joan L. Luby, Ryan Bogdan, Arpana Agrawal, Michael S. Gaffrey, Andrew C. Belden, Kelly N. Botteron, Michael P. Harms, and Deanna M. Barch Washington University in St. Louis Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic- pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N ϭ 120). Whole-brain regression analyses indicated that increasing genetic “risk” predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic “risk” and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation.
    [Show full text]
  • The Claustrum: Three-Dimensional Reconstruction, Photorealistic Imaging, and Stereotactic Approach
    Folia Morphol. Vol. 70, No. 4, pp. 228–234 Copyright © 2011 Via Medica O R I G I N A L A R T I C L E ISSN 0015–5659 www.fm.viamedica.pl The claustrum: three-dimensional reconstruction, photorealistic imaging, and stereotactic approach S. Kapakin Department of Anatomy, Faculty of Medicine, Atatürk University, Erzurum, Turkey [Received 7 July 2011; Accepted 25 September 2011] The purpose of this study was to reveal the computer-aided three-dimensional (3D) appearance, the dimensions, and neighbourly relations of the claustrum and make a stereotactic approach to it by using serial sections taken from the brain of a human cadaver. The Snake technique was used to carry out 3D reconstructions of the claustra and surrounding structures. The photorealistic imaging and stereo- tactic approach were rendered by using the Advanced Render Module in Cinema 4D software. The claustrum takes the form of the concavity of the insular cortex and the convexity of the putamen. The inferior border of the claustrum is at about the same level as the bottom edge of the insular cortex and the putamen, but the superior border of the claustrum is at a lower level than the upper edge of the insular cortex and the putamen. The volume of the right claustrum, in the dimen- sions of 35.5710 mm ¥ 1.0912 mm ¥ 16.0000 mm, was 828.8346 mm3, and the volume of the left claustrum, in the dimensions of 32.9558 mm ¥ 0.8321 mm ¥ ¥ 19.0000 mm, was 705.8160 mm3. The surface areas of the right and left claustra were calculated to be 1551.149697 mm2 and 1439.156450 mm2 by using Surf- driver software.
    [Show full text]
  • HHS Public Access Author Manuscript
    HHS Public Access Author manuscript Author Manuscript Author ManuscriptNeuroscience Author Manuscript. Author manuscript; Author Manuscript available in PMC 2015 April 26. Published in final edited form as: Neuroscience. 2012 December 13; 226: 145–155. doi:10.1016/j.neuroscience.2012.09.011. The Distribution of Phosphodiesterase 2a in the Rat Brain D. T. Stephensona,†, T. M. Coskranb, M. P. Kellya,‡, R. J. Kleimana,§, D. Mortonc, S. M. O'neilla, C. J. Schmidta, R. J. Weinbergd, and F. S. Mennitia,* D. T. Stephenson: [email protected]; M. P. Kelly: [email protected]; R. J. Kleiman: [email protected]; F. S. Menniti: [email protected] aNeuroscience Biology, Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA bInvestigative Pathology, Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA cToxologic Pathology, Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA dDepartment of Cell Biology & Physiology, Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA Abstract The phosphodiesterases (PDEs) are a superfamily of enzymes that regulate spatio-temporal signaling by the intracellular second messengers cAMP and cGMP. PDE2A is expressed at high levels in the mammalian brain. To advance our understanding of the role of this enzyme in regulation of neuronal signaling, we here describe the distribution of PDE2A in the rat brain. PDE2A mRNA was prominently expressed in glutamatergic pyramidal cells in cortex, and in pyramidal and dentate granule cells in the hippocampus. Protein concentrated in the axons and nerve terminals of these neurons; staining was markedly weaker in the cell bodies and proximal dendrites.
    [Show full text]
  • Motor Systems Basal Ganglia
    Motor systems 409 Basal Ganglia You have just read about the different motor-related cortical areas. Premotor areas are involved in planning, while MI is involved in execution. What you don’t know is that the cortical areas involved in movement control need “help” from other brain circuits in order to smoothly orchestrate motor behaviors. One of these circuits involves a group of structures deep in the brain called the basal ganglia. While their exact motor function is still debated, the basal ganglia clearly regulate movement. Without information from the basal ganglia, the cortex is unable to properly direct motor control, and the deficits seen in Parkinson’s and Huntington’s disease and related movement disorders become apparent. Let’s start with the anatomy of the basal ganglia. The important “players” are identified in the adjacent figure. The caudate and putamen have similar functions, and we will consider them as one in this discussion. Together the caudate and putamen are called the neostriatum or simply striatum. All input to the basal ganglia circuit comes via the striatum. This input comes mainly from motor cortical areas. Notice that the caudate (L. tail) appears twice in many frontal brain sections. This is because the caudate curves around with the lateral ventricle. The head of the caudate is most anterior. It gives rise to a body whose “tail” extends with the ventricle into the temporal lobe (the “ball” at the end of the tail is the amygdala, whose limbic functions you will learn about later). Medial to the putamen is the globus pallidus (GP).
    [Show full text]
  • The Hippocampus and Dorsolateral Striatum Integrate Distinct Types of Memories Through Time and Space, Respectively
    The Journal of Neuroscience, November 18, 2020 • 40(47):9055–9065 • 9055 Behavioral/Cognitive The Hippocampus and Dorsolateral Striatum Integrate Distinct Types of Memories through Time and Space, Respectively Janina Ferbinteanu Departments of Physiology and Pharmacology, and Neurology, SUNY Downstate Medical Center, Brooklyn, New York 11203 Several decades of research have established that different kinds of memories result from the activity of discrete neural net- works. Studying how these networks process information in experiments that target specific types of mnemonic representa- tions has provided deep insights into memory architecture and its neural underpinnings. However, in natural settings reality confronts organisms with problems that are not neatly compartmentalized. Thus, a critical problem in memory research that still needs to be addressed is how distinct types of memories are ultimately integrated. Here we demonstrate how two mem- ory networks, the hippocampus and dorsolateral striatum, may accomplish such a goal. The hippocampus supports memory for facts and events, collectively known as declarative memory and often studied as spatial memory in rodents. The dorsolat- eral striatum provides the basis for habits that are assessed in stimulus–response types of tasks. Expanding previous findings, the current work revealed that in male Long–Evans rats, the hippocampus and dorsolateral striatum use time and space in distinct and largely complementary ways to integrate spatial and habitual representations. Specifically, the hippocampus sup- ported both types of memories when they were formed in temporal juxtaposition, even if the learning took place in different environments. In contrast, the lateral striatum supported both types of memories if they were formed in the same environ- ment, even at temporally distinct points.
    [Show full text]
  • Brain Anatomy
    BRAIN ANATOMY Adapted from Human Anatomy & Physiology by Marieb and Hoehn (9th ed.) The anatomy of the brain is often discussed in terms of either the embryonic scheme or the medical scheme. The embryonic scheme focuses on developmental pathways and names regions based on embryonic origins. The medical scheme focuses on the layout of the adult brain and names regions based on location and functionality. For this laboratory, we will consider the brain in terms of the medical scheme (Figure 1): Figure 1: General anatomy of the human brain Marieb & Hoehn (Human Anatomy and Physiology, 9th ed.) – Figure 12.2 CEREBRUM: Divided into two hemispheres, the cerebrum is the largest region of the human brain – the two hemispheres together account for ~ 85% of total brain mass. The cerebrum forms the superior part of the brain, covering and obscuring the diencephalon and brain stem similar to the way a mushroom cap covers the top of its stalk. Elevated ridges of tissue, called gyri (singular: gyrus), separated by shallow groves called sulci (singular: sulcus) mark nearly the entire surface of the cerebral hemispheres. Deeper groves, called fissures, separate large regions of the brain. Much of the cerebrum is involved in the processing of somatic sensory and motor information as well as all conscious thoughts and intellectual functions. The outer cortex of the cerebrum is composed of gray matter – billions of neuron cell bodies and unmyelinated axons arranged in six discrete layers. Although only 2 – 4 mm thick, this region accounts for ~ 40% of total brain mass. The inner region is composed of white matter – tracts of myelinated axons.
    [Show full text]