DOCSLIB.ORG

Functional Roles of Neurotransmitters and Neuromodulators in the Dorsal Striatum

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Downloaded from learnmem.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Review Functional roles of neurotransmitters and neuromodulators in the dorsal striatum Jeehaeh Do,1 Jae-Ick Kim,2 Joseph Bakes,1 Kyungmin Lee,3 and Bong-Kiun Kaang1,2,4 1Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea; 2National Creative Research Initiative Center for Memory, Department of Biological Sciences, College of Natural Sciences, Seoul, National University, Seoul 151-747, Korea; 3Department of Anatomy, School of Medicine, Kyungpook National University, 2-101 Dongin-Dong, Daegu 700-842, Korea The dorsal striatum, with its functional microcircuits galore, serves as the primary gateway of the basal ganglia and is known to play a key role in implicit learning. Initially, excitatory inputs from the cortex and thalamus arrive on the direct and indirect pathways, where the precise flow of information is then regulated by local GABAergic interneurons. The balance of excitatory and inhibitory transmission in the dorsal striatum is modulated by neuromodulators such as dopa- mine and acetylcholine. Under pathophysiological states in the dorsal striatum, an alteration in excitatory and inhibitory transmission may underlie dysfunctional motor control. Here, we review the cellular connections and modulation of striatal microcircuits and propose that modulating the excitatory and inhibitory balance in synaptic transmission of the dorsal stri- atum is important for regulating locomotion. The dorsal striatum is best known for its role in decision-making, such as attention deficit/hyperactivity disorder (ADHD) and especially in action selection and initiation through the conver- autism. gence of sensorimotor, cognitive, and motivational information (DeLong 1990; Smith et al. 1998; Balleine et al. 2007). As the pri- mary input of the basal ganglia, the striatum receives glutamater- Circuits: Glutamatergic and GABAergic transmission gic inputs from the cortex and thalamus and in turn projects GABAergic outputs to the globus pallidus and substantia nigra Corticostriatal circuit: Direct/indirect pathway pars reticulata (SNr). Inputs from the cortex and thalamus both MSNs constitute .90% of the dense GABAergic striatal neuron form excitatory synaptic connections on medium spiny neurons population and can be subdivided into two main classes: the (MSN) in which cortical afferents are from the sensory, motor, direct-pathway (striatonigral) and indirect-pathway (striatopalli- and associational cortex (Bolam et al. 2000), and thalamic affer- dal) MSNs. The striatonigral MSNs (D -MSN) express high levels ents are from the intralaminar thalamic nuclei (Doig et al. 1 of both D dopamine (DA) receptors and M4 muscarinic receptors 2010). These glutamatergic inputs are then processed in the dorsal 1 and project directly to the internal globus pallidus (GPi in pri- striatum where numerous connections between various types of mates, GPm in rodents) and SNr. Striatopallidal MSNs (D -MSN) neurons exist. Thus, the complexity of neuronal circuits has 2 highly express D dopamine receptors and adenosine A recep- made it difficult to elucidate the functional roles of the striatum. 2 2A tors and project to the external globus pallidus (GPe in primates, Recently, studies focused on interneurons that reside in the dorsal GP in rodents). Direct and indirect pathways act in opposition striatum have characterized the physiological features and func- to one another to control movement, which indicates segregat- tional connections. For example, parvalbumin-expressing fast- ed information processing (Albin et al. 1989; DeLong 1990). spiking interneurons (PV-FSI) and neuropeptide-Y positive low- Compelling evidence of this segregation has been obtained from threshold spiking interneurons (NPY-LTS) form synaptic connec- studies in bacterial artificial chromosome (BAC) transgenic mice tions with MSNs and regulate the firing activity of the principal (Gong et al. 2003). The existence of synaptic connections between neuron MSNs (Koos and Tepper 1999; Gittis et al. 2010; direct- and indirect-pathway MSNs was reported only recently. Chuhma et al. 2011). These interneurons were shown to have dis- However, the functional significance of these connections is yet tinct firing patterns and connections, and thus they may exert to be characterized. different effects on MSNs. Other crucial connections are the cho- Cell-type specific whole-cell voltage clamp recordings have linergic, dopaminergic, and serotonergic axons that strongly in- revealed distinct physiological properties in D - and D -MSNs in nervate the dorsal striatum. These projections are essential for 1 2 BAC transgenic mice. D -MSNs have a higher NMDA/AMPA (2- modulating striatal circuits and disruption of such signaling can 2 amino-3-hydroxy-5-methyl-4-isoxazol propionic acid/N-Methyl- result in movement impairments and neurological disorders D-aspartate) ratio. Also, a greater paired-pulse ratio (PPR) value such as Huntington’s disease (Lovinger 2010). This review sum- than that of D -MSN indicates that corticostriatal inputs to marizes recent reports of the microcircuits present in the dorsal 1 D -MSNs have a higher probability in neurotransmitter release striatum, although serotonergic signaling is excluded, and sug- 2 (Ding et al. 2008). Further, membranes of D -MSNs are intrinsical- gests a putative role for striatal microcircuits in motor dysfunction 2 ly more excitable than those of D -MSNs (Kreitzer and Malenka and/or hyperactivity that often accompany psychiatric disorders 1 2007), which is supported by an anatomical comparison of soma- 4 todendritic trees, where the surface area of D1-MSNs is larger than Corresponding author that of D -MSNs (Gertler et al. 2008). E-mail [email protected] 2 Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.025015.111. Once the striatonigral direct-pathway circuit receives glu- Freely available online through the Learning & Memory Open Access option. tamatergic inputs from the sensorimotor cortex, GABAergic 20:21–28 # 2013 Cold Spring Harbor Laboratory Press 21 Learning & Memory ISSN 1549-5485/13; www.learnmem.org Downloaded from learnmem.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Microcircuits in dorsal striatum and hyperactivity D1-MSNs, which project directly to GABAergic neurons in the GPi Local GABAergic circuits: Parvalbumin-expressing and SNr, are activated. Thus, GABAergic GPi and SNr neurons, fast-spiking interneurons and neuropeptide-Y positive which in turn send axons to motor nuclei of the thalamus, low-threshold spiking interneurons become inhibited. The net effect of this information flow is a disinhibition of excitatory thalamocortical projections. Since The GABAergic interneurons in the striatum form feed-forward the GPi is involved in axial and limb movements and the SNr in inhibitory synaptic connections on both MSNs and neighboring head and eye movements, activation of the striatonigral path- interneurons (Ding et al. 2010). The neighboring interneurons way is predicted to promote action selection and movement. have been largely classified into two groups: parvalbumin positive The striatopallidal indirect-pathway circuit also receives gluta- fast-spiking interneurons (PV-FSI) and neuropeptide-Y expressing matergic inputs from the cortex. Glutamatergic input onto low-threshold spiking interneurons (NPY-LTS). Although inter- GABAergic D2-MSNs inhibits GABAergic pallidal neurons of the neurons constitute a very small population of the dorsal striatum GPe, whereupon the target of the GPe neurons, the glutamatergic compared to that of MSNs, the minority exerts powerful inhibito- neurons of the subthalamic nucleus (STN), are disinhibited. ry effects on MSNs through GABAergic transmission. Studies have Disinhibition of excitatory STN neurons could activate inhib- shown that FSIs form multiple synapses, roughly ranging from itory output neurons of the GPi and SNr, resulting in a net effect 135 to 541 in number, on MSNs. One FSI could delay the genera- of an inhibition of excitatory thalamocortical projection neurons. tion of action potentials in MSNs by a single inhibitory postsynap- This would then lead to a reduction of cortical premotor drive tic current (IPSC) (Koos and Tepper 1999). FSIs both receive and inhibition of movement. and respond to cortical input faster than MSNs (Kawaguchi A compelling number of studies of synaptic plasticity in 1993), and in turn can exert fast inhibitory actions on both types corticostriatal synapses have been reported, but an in-depth of MSNs (Planert et al. 2010). BAC transgenic mice in which examination of these studies is beyond the scope of this review. GABAergic interneurons can be identified showed that FSIs prefer- Long-term depression (LTD), long-term potentiation (LTP), and entially target direct-pathway MSNs over indirect-pathway MSNs spike-timing dependent plasticity (STDP) occur in these types (Gittis et al. 2010). In addition, it is important to note that there is of synapses (Calabresi et al. 1992a,b; Centonze et al. 2001; Fino a prominent distinction between the actions of GABAA receptors et al. 2005; Wang et al. 2006; Pawlak and Kerr 2008). Endocanna- in direct- and indirect-pathway MSNs; currents through GABAA binoid-dependent LTD (Gerdeman et al. 2002) is much better receptors always depressed the response to corticostriatal stimula- characterized than NMDAR-dependent or NMDAR-independent tion
Recommended publications
  • Original Article the Acute E€Ects of Continuous and Conditional

    Original Article the Acute E€Ects of Continuous and Conditional

    Spinal Cord (2001) 39, 420 ± 428 ã 2001 International Medical Society of Paraplegia All rights reserved 1362 ± 4393/01 $15.00 www.nature.com/sc Original Article The acute eects of continuous and conditional neuromodulation on the bladder in spinal cord injury APS Kirkham*,1, NC Shah1, SL Knight1, PJR Shah1 and MD Craggs1 1Neuroprostheses Research Centre, Royal National Orthopaedic Hospital, Stanmore, Middlesex HA7 4LP, UK Study design: Laboratory investigation using serial slow-®ll cystometrograms. Objectives: To examine the acute eects of dierent modes of dorsal penile nerve stimulation on detrusor hyperre¯exia, bladder capacity and bladder compliance in spinal cord injury (SCI). Setting: Spinal Injuries Unit, Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK. Methods: Fourteen SCI patients were examined. Microtip transducer catheters enabled continuous measurement of anal sphincter, urethral sphincter and intravesical pressures. Control cystometrograms were followed by stimulation of the dorsal penile nerve at 15 Hz, 200 ms pulse width and amplitude equal to twice that which produced a pudendo-anal re¯ex. Stimulation was either continuous or in bursts of one minute triggered by a rise in detrusor pressure of 10 cm water (conditional). Further control cystometrograms were then performed to examine the residual eects of stimulation. Results: Bladder capacity increased signi®cantly during three initial control ®lls. Continuous stimulation (n=6) signi®cantly increased bladder capacity by a mean of 110% (+Standard Deviation 85%) or 173 ml (+146 ml), and bladder compliance by a mean of 53% (+31%). Conditional stimulation in a dierent group of patients (n=6) signi®cantly increased bladder capacity, by 144% (+127%) or 230 ml (+143 ml).
  • Nucleus Accumbens Medium Spiny Neurons Subtypes Signal Both Reward and Aversion

    Nucleus Accumbens Medium Spiny Neurons Subtypes Signal Both Reward and Aversion

    Molecular Psychiatry https://doi.org/10.1038/s41380-019-0484-3 ARTICLE Nucleus accumbens medium spiny neurons subtypes signal both reward and aversion 1,2 1,2,3,4 1,2 1,2 Carina Soares-Cunha ● Nivaldo A. P. de Vasconcelos ● Bárbara Coimbra ● Ana Verónica Domingues ● 1,2 1,2 1,2,5,6 1,2 1,2,7 Joana M. Silva ● Eduardo Loureiro-Campos ● Rita Gaspar ● Ioannis Sotiropoulos ● Nuno Sousa ● Ana João Rodrigues 1,2,7 Received: 25 June 2018 / Revised: 14 May 2019 / Accepted: 20 June 2019 © The Author(s) 2019. This article is published with open access Abstract Deficits in decoding rewarding (and aversive) signals are present in several neuropsychiatric conditions such as depression and addiction, emphasising the importance of studying the underlying neural circuits in detail. One of the key regions of the reward circuit is the nucleus accumbens (NAc). The classical view on the field postulates that NAc dopamine receptor D1- expressing medium spiny neurons (D1-MSNs) convey reward signals, while dopamine receptor D2-expressing MSNs (D2- MSNs) encode aversion. Here, we show that both MSN subpopulations can drive reward and aversion, depending on their 1234567890();,: 1234567890();,: neuronal stimulation pattern. Brief D1- or D2-MSN optogenetic stimulation elicited positive reinforcement and enhanced cocaine conditioning. Conversely, prolonged activation induced aversion, and in the case of D2-MSNs, decreased cocaine conditioning. Brief stimulation was associated with increased ventral tegmenta area (VTA) dopaminergic tone either directly (for D1-MSNs) or indirectly via ventral pallidum (VP) (for D1- and D2-MSNs). Importantly, prolonged stimulation of either MSN subpopulation induced remarkably distinct electrophysiological effects in these target regions.
  • TAK-063, a PDE10A Inhibitor with Balanced Activation of Direct and Indirect Pathways, Provides Potent Antipsychotic-Like Effects in Multiple Paradigms

    TAK-063, a PDE10A Inhibitor with Balanced Activation of Direct and Indirect Pathways, Provides Potent Antipsychotic-Like Effects in Multiple Paradigms

    Neuropsychopharmacology (2016) 41, 2252–2262 © 2016 American College of Neuropsychopharmacology. All rights reserved 0893-133X/16 www.neuropsychopharmacology.org TAK-063, a PDE10A Inhibitor with Balanced Activation of Direct and Indirect Pathways, Provides Potent Antipsychotic-Like Effects in Multiple Paradigms 1 1 1 1,2 ,1 Kazunori Suzuki , Akina Harada , Hirobumi Suzuki , Maki Miyamoto and Haruhide Kimura* 1 2 CNS Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Japan; Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Japan Phosphodiesterase 10A (PDE10A) inhibitors are expected to be novel drugs for schizophrenia through activation of both direct and indirect pathway medium spiny neurons. However, excess activation of the direct pathway by a dopamine D receptor agonist SKF82958 1 canceled antipsychotic-like effects of a dopamine D receptor antagonist haloperidol in methamphetamine (METH)-induced hyperactivity 2 in rats. Thus, balanced activation of these pathways may be critical for PDE10A inhibitors. Current antipsychotics and the novel PDE10A inhibitor TAK-063, but not the selective PDE10A inhibitor MP-10, produced dose-dependent antipsychotic-like effects in METH-induced hyperactivity and prepulse inhibition in rodents. TAK-063 and MP-10 activated the indirect pathway to a similar extent; however, MP-10 caused greater activation of the direct pathway than did TAK-063. Interestingly, the off-rate of TAK-063 from PDE10A in rat brain sections was faster than that of MP-10, and a slower off-rate PDE10A inhibitor with TAK-063-like chemical structure showed an MP-10-like pharmacological profile. In general, faster off-rate enzyme inhibitors are more sensitive than slower off-rate inhibitors to binding inhibition by enzyme substrates.
  • A Proposed Neural Pathway for Vocalization in South African Clawed Frogs, Xenopus Laevis

    A Proposed Neural Pathway for Vocalization in South African Clawed Frogs, Xenopus Laevis

    Journal of J Comp Physiol A (1985) 157:749-761 Sensory, Comparative and.ou~,, Physiology A Physiology~h.v,or* Springer-Verlag 1985 A proposed neural pathway for vocalization in South African clawed frogs, Xenopus laevis Daniel M. Wetzel*, Ursula L. Haerter*, and Darcy B. Kelley** Program in Neuroscience, Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA, and Department of Biological Sciences, Columbia University, New York, New York 10027, USA Accepted September 9, 1985 Summary. 1. Vocalizations of South African 3. Injection of HRP-WGA into DTAM re- clawed frogs are produced by contractions of la- sulted in labelled cells in the striatum, preoptic area ryngeal muscles innervated by motor neurons of and thalamus. Posterior to DTAM, labelled cells the caudal medulla (within cranial nerve nucleus were found in the rhombencephalic reticular nuclei IX-X). We have traced afferents to laryngeal mo- as well as n. IX-X of males. Results in females tor neurons in male and female frogs using retro- were similar with the exception that n. IX-X la- grade axonal transport of horseradish peroxidase belled cells were only seen after very large injec- conjugated to wheat germ agglutinin (HRP- tions of unconjugated HRP into DTAM and sur- WGA). rounding tegmentum. Thus, the projection of n. 2. After iontophoretic injection of HRP-WGA IX-X neurons to DTAM is not as robust in fe- into n. IX-X, retrogradely labelled neurons were males as males. seen in the contralateral n. IX-X, in rhombence- 4. These anatomical studies revealed candidate phalic reticular nuclei, and in the pre-trigeminal brain nuclei contributing to the generation of vocal nucleus of the dorsal tegmental area (DTAM) of behaviors and confirmed some features of a model both males and females.
  • Selective Neural Pathway Targeting Reveals Key Roles of Thalamostriatal Projection in the Control of Visual Discrimination

    Selective Neural Pathway Targeting Reveals Key Roles of Thalamostriatal Projection in the Control of Visual Discrimination

    The Journal of Neuroscience, November 23, 2011 • 31(47):17169–17179 • 17169 Behavioral/Systems/Cognitive Selective Neural Pathway Targeting Reveals Key Roles of Thalamostriatal Projection in the Control of Visual Discrimination Shigeki Kato,1 Masahito Kuramochi,1,2 Kenta Kobayashi,1 Ryoji Fukabori,1 Kana Okada,1,2 Motokazu Uchigashima,3 Masahiko Watanabe,3 Yuji Tsutsui,4 and Kazuto Kobayashi1,2 1Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan, 2Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan, 3Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan, and 4Faculty of Symbiotic Systems Science, Fukushima University, Fukushima 960-1296, Japan The dorsal striatum receives converging excitatory inputs from diverse brain regions, including the cerebral cortex and the intralaminar/ midline thalamic nuclei, and mediates learning processes contributing to instrumental motor actions. However, the roles of each striatal input pathway in these learning processes remain uncertain. We developed a novel strategy to target specific neural pathways and applied this strategy for studying behavioral roles of the pathway originating from the parafascicular nucleus (PF) and projecting to the dorso- lateral striatum. A highly efficient retrograde gene transfer vector encoding the recombinant immunotoxin (IT) receptor was injected into the dorsolateral striatum in mice to express the receptor in neurons innervating the striatum. IT treatment into the PF of the vector-injected animals caused a selective elimination of neurons of the PF-derived thalamostriatal pathway. The elimination of this pathway impaired the response selection accuracy and delayed the motor response in the acquisition of a visual cue-dependent discrim- ination task.
  • Central Neurocircuits Regulating Food Intake in Response to Gut Inputs—Preclinical Evidence

    Central Neurocircuits Regulating Food Intake in Response to Gut Inputs—Preclinical Evidence

    nutrients Review Central Neurocircuits Regulating Food Intake in Response to Gut Inputs—Preclinical Evidence Kirsteen N. Browning * and Kaitlin E. Carson Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-717-531-8267 Abstract: The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) via the sensory afferent vagus nerve. This vast volume of complex sensory information is received by neurons of the nucleus of the tractus solitarius (NTS) and is integrated with responses to circulating factors as well as descending inputs from the brainstem, midbrain, and forebrain nuclei involved in autonomic regulation. The integrated signal is relayed to the adjacent dorsal motor nucleus of the vagus (DMV), which supplies the motor output response via the efferent vagus nerve to regulate and modulate gastric motility, tone, secretion, and emptying, as well as intestinal motility and transit; the precise coordination of these responses is essential for the control of meal size, meal termination, and nutrient absorption. The interconnectivity of the NTS implies that many other CNS areas are capable of modulating vagal efferent output, emphasized by the many CNS disorders associated with dysregulated GI functions including feeding. This review will summarize the role of major CNS centers to gut-related inputs in the regulation of gastric function Citation: Browning, K.N.; Carson, with specific reference to the regulation of food intake.
  • Addiction Becomes Meeting Report a Brain Disease

    Addiction Becomes Meeting Report a Brain Disease

    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Neuron, Vol. 26, 27±33, April, 2000, Copyright 2000 by Cell Press Addiction Becomes Meeting Report a Brain Disease Roy A. Wise* discriminative and executive functions of the medial pre- Intramural Research Program frontal cortex, the amygdala, and the hippocampus. A National Institute on Drug Abuse number of imaging studies suggested multiple cortical Baltimore, Maryland 21224 and subcortical structures that participate both in drug reward and in more natural motivational phenomena. For example, Hans Breiter (Massachusetts General Hos- At the end of the decade of the brain, the study of pital) showed functional magnetic resonance imaging neural mechanisms has come to dominate the study (fMRI) data implicating a generalized limbic and cortical of addiction. Whereas attention was once on somatic reward circuitry, stressing the nucleus accumbens and withdrawal symptoms and liver enzymes, it has turned sublenticular amygdala, in common aspects of drug (co- to reward circuitry in the brain and to neuroadaptations caine and morphine) reward and monetary rewards and in that circuitry that can change sensitivity to addictive in subjective probability assessment. These findings en- drugs and that, it is hoped, can explain the compulsive courage hypotheses about commonalities between the dimension of drug seeking in addicts. The focus on brain brain mechanisms of addiction and gambling. His data mechanisms of reward and addiction began with the implicate this circuitry in drug and nondrug reward ex- discoveries of brain reward circuitry in the 1950s and pectation as well as in drug and nondrug reward.
  • Structural Plasticity Associated with Exposure to Drugs of Abuse

    Structural Plasticity Associated with Exposure to Drugs of Abuse

    Neuropharmacology 47 (2004) 33–46 www.elsevier.com/locate/neuropharm Structural plasticity associatedwith exposure to drugsof abuse Terry E. Robinson a,Ã, Bryan Kolb b a Department of Psychology (Biopsychology) and Neuroscience Program, The University of Michigan, 525 E. University (East Hall), Ann Arbor, MI 48109, USA b Department of Psychology and Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alta., Canada T1K 3M4 Received19 April 2004; receivedin revisedform 24 May 2004; accepted30 June 2004 Abstract Persistent changes in behavior andpsychological function that occur as a function of experience, such those associatedwith learning andmemory, are thought to be dueto the reorganization of synaptic connections (structural plasticity) in relevant brain circuits. Some of the most compelling examples of experience-dependent changes in behavior and psychological function, changes that can last a lifetime, are those that accrue with the development of addictions. However, until recently, there has been almost no research on whether potentially addictive drugs produce forms of structural plasticity similar to those associated with other forms of experience-dependent plasticity. In this paper we summarize evidence that, indeed, exposure to amphetamine, cocaine, nicotine or morphine produces persistent changes in the structure of dendrites and dendritic spines on cells in brain regions involvedin incentive motivation andreward(such as the nucleus accumbens), andjudgmentandthe inhibitory control of beha- vior (such as the prefrontal cortex). It is suggestedthat structural plasticity associatedwith exposure to drugsof abuse reflects a reorganization of patterns of synaptic connectivity in these neural systems, a reorganization that alters their operation, thus con- tributing to some of the persistent sequela associated with drug use—including addiction.
  • The Five Neural Pathways of Memory HU Jian-Feng

    The Five Neural Pathways of Memory HU Jian-Feng

    5th International Conference on Education, Management, Information and Medicine (EMIM 2015) The five neural pathways of memory HU Jian-feng Institute of Information Technology, Jiangxi University of Technology, Nanchang 330098, China Keywords: Memory; Neuron; Learning; Brain Abstract: All the acquisition of knowledge is a memory, the memory is the foundation of all intellectual activities. Memory is also the basis of education. This paper presents five neural pathways of memory, respectively, based on information, rules, concepts, expectations and integration. These pathways has important significance on the formation and maintain of memory. Understanding these is very helpful to improve education. Introduction Memory is the results of modified synaptic transmission. The most prominent bottleneck to understand the mechanisms of memory is the connection structure of fine synapses. However, we still don't know how to connect the brain nerve, how synaptic connection work between what the specific types of neurons, and how synaptic connections modify. The lack of effective research method is important to explore the mechanism of memory, such as brain imaging device resolution and coverage is a contradiction, high resolution is often limited coverage, large coverage often insufficient resolution. Based on combining the various models of learning and memory, combined with some cases of pathological or genius, this paper proposes five neural pathway of memory. Pathway one: Memory based on information (the basis of information transmission) The input data are some sophisticated audio-visual information, following cognitive learning mechanism, then through neural pathway of audio-visual information processing, finally to realize the access of cognitive information by the area of cortex.
  • Pathway-Specific Control of Reward Learning and Its Flexibility Via Selective Dopamine Receptors in the Nucleus Accumbens

    Pathway-Specific Control of Reward Learning and Its Flexibility Via Selective Dopamine Receptors in the Nucleus Accumbens

    Pathway-specific control of reward learning and its flexibility via selective dopamine receptors in the nucleus accumbens Satoshi Yawata, Takashi Yamaguchi, Teruko Danjo, Takatoshi Hikida1, and Shigetada Nakanishi2 Department of Systems Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan Contributed by Shigetada Nakanishi, June 26, 2012 (sent for review June 6, 2012) In the basal ganglia, inputs from the nucleus accumbens (NAc) are is reversibly blocked in a doxycycline-regulated manner (13–15). transmitted through both direct and indirect pathways and control In this technique, the transmission-blocking tetanus toxin is reward-based learning. In the NAc, dopamine (DA) serves as a key expressed in a pathway-specific and doxycycline-regulated man- neurotransmitter, modulating these two parallel pathways. This ner, thus allowing separate and reversible blockade of neuro- study explored how reward learning and its flexibility are controlled transmission in the direct pathway (D-RNB mice) or the indirect in a pathway-specific and DA receptor-dependent manner. We used pathway (I-RNB mice) in vivo (15, 16). The function of the basal two techniques (i) reversible neurotransmission blocking (RNB), in ganglia circuitry becomes defective only when both sides of the which transmission of the direct (D-RNB) or the indirect pathway basal ganglia circuit are simultaneously impaired in the brain (I-RNB) in the NAc on both sides of the hemispheres was selectively hemispheres (17, 18). We thus extended the RNB technique to blocked by transmission-blocking tetanus toxin; and (ii) asymmetric an asymmetric RNB (aRNB) technique, in which one side of the RNB, in which transmission of the direct (D-aRNB) or the indirect path- basal ganglia circuit is blocked by the RNB technique, and the way (I-aRNB) was unilaterally blocked by RNB techniques and the other intact side is treated with an agonist or antagonist specific intact side of the NAc was infused with DA agonists or antagonists.
  • Egr-1 Induces DARPP-32 Expression in Striatal Medium Spiny Neurons Via a Conserved Intragenic Element

    Egr-1 Induces DARPP-32 Expression in Striatal Medium Spiny Neurons Via a Conserved Intragenic Element

    Thomas Jefferson University Jefferson Digital Commons Farber Institute for Neurosciences Faculty Papers Farber Institute for Neurosciences 5-16-2012 Egr-1 induces DARPP-32 expression in striatal medium spiny neurons via a conserved intragenic element. Serene Keilani Departments of Neurology and Pediatrics, Mount Sinai School of Medicine, New York Samira Chandwani Departments of Neurology and Pediatrics, Mount Sinai School of Medicine, New York Georgia Dolios Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York Alexey Bogush Weinberg Unit for ALS Research, Department of Neuroscience, Farber Institute for Neuroscience, Thomas Jefferson University Follow this and additional works at: https://jdc.jefferson.edu/farberneursofp Heike Beck Walter Par Brt ofendel the NeurCenterology of Experimental Commons Medicine, Ludwig Maximilians University Let us know how access to this document benefits ouy See next page for additional authors Recommended Citation Keilani, Serene; Chandwani, Samira; Dolios, Georgia; Bogush, Alexey; Beck, Heike; Hatzopoulos, Antonis K; Rao, Gadiparthi N; Thomas, Elizabeth A; Wang, Rong; and Ehrlich, Michelle E, "Egr-1 induces DARPP-32 expression in striatal medium spiny neurons via a conserved intragenic element." (2012). Farber Institute for Neurosciences Faculty Papers. Paper 16. https://jdc.jefferson.edu/farberneursofp/16 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship.
  • In Vivo Imaging Identifies Temporal Signature of D1 and D2 Medium Spiny Neurons in Cocaine Reward

    In Vivo Imaging Identifies Temporal Signature of D1 and D2 Medium Spiny Neurons in Cocaine Reward

    In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward Erin S. Caliparia, Rosemary C. Bagota, Immanuel Purushothamana, Thomas J. Davidsonb, Jordan T. Yorgasonc, Catherine J. Peñaa, Deena M. Walkera, Stephen T. Pirpiniasa, Kevin G. Guisea, Charu Ramakrishnanb, Karl Deisserothb,d,e, and Eric J. Nestlera,1 aFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; bDepartment of Bioengineering, Stanford University, Stanford, CA 94305; cVollum Institute, Oregon Health and Science University, Portland, OR 97239; dHoward Hughes Medical Institute, Stanford University, Stanford, CA 94305; and eDepartment of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305 Edited by Susan G. Amara, National Institutes of Health, Bethesda, MD, and approved January 8, 2016 (received for review October 27, 2015) The reinforcing and rewarding properties of cocaine are attributed largely nonoverlapping populations of medium spiny neurons to its ability to increase dopaminergic transmission in nucleus (MSNs) (13). These two subtypes of MSNs exert opposite effects accumbens (NAc). This action reinforces drug taking and seeking on behavior, with optogenetic activation of D1-type neurons pro- and leads to potent and long-lasting associations between the moting positive reinforcement and increasing the formation of – rewarding effects of the drug and the cues associated with its cocaine reward context associations and activation of D2-type availability. The inability to extinguish these associations is a key factor neurons being aversive and decreasing cocaine reward (14, 15); contributing to relapse. Dopamine produces these effects by control- related differences in behavioral responses are seen in response to ling the activity of two subpopulations of NAc medium spiny neurons D1 vs.