Monitoring cholinergic activity during attentional performance in mice heterozygous for the choline transporter: a model of cholinergic capacity limits.


:Reductions in the capacity of the human choline transporter (SLC5A7, CHT) have been hypothesized to diminish cortical cholinergic neurotransmission, leading to risk for cognitive and mood disorders. To determine the acetylcholine (ACh) release capacity of cortical cholinergic projections in a mouse model of cholinergic hypofunction, the CHT+/- mouse, we assessed extracellular ACh levels while mice performed an operant sustained attention task (SAT). We found that whereas SAT-performance-associated increases in extracellular ACh levels of CHT+/- mice were significantly attenuated relative to wildtype littermates, performance on the SAT was normal. Tetrodotoxin-induced blockade of neuronal excitability reduced both dialysate ACh levels and SAT performance similarly in both genotypes. Likewise, lesions of cholinergic neurons abolished SAT performance in both genotypes. However, cholinergic activation remained more vulnerable to the reverse-dialyzed muscarinic antagonist atropine in CHT+/- mice. Additionally, CHT+/- mice displayed greater SAT-disrupting effects of reverse dialysis of the nAChR antagonist mecamylamine. Receptor binding assays revealed a higher density of α4β2* nAChRs in the cortex of CHT+/- mice compared to controls. These findings reveal compensatory mechanisms that, in the context of moderate cognitive challenges, can overcome the performance deficits expected from the significantly reduced ACh capacity of CHT+/- cholinergic terminals. Further analyses of molecular and functional compensations in the CHT+/- model may provide insights into both risk and resiliency factors involved in cognitive and mood disorders.






Paolone G,Mallory CS,Cherian AK,Miller TR,Blakely RD,Sarter M




Has Abstract


2013-12-01 00:00:00










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    pub_type: 杂志文章


    authors: Mañé N,Jiménez-Sábado V,Jiménez M

    更新日期:2016-11-01 00:00:00

  • Differential effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on various 5-HT receptor binding sites in the rat brain.

    abstract::The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an alkylating agent producing irreversible blockade of various membrane bound receptors in brain, were investigated on four different types of serotonin receptors, 5-HT1A, 5-HT1B, 5-HT2A and 5-HT3, in various brain regions in the rat. In addition, t...


    pub_type: 杂志文章


    authors: Gozlan H,Laporte AM,Thibault S,Schechter LE,Bolaños F,Hamon M

    更新日期:1994-03-01 00:00:00

  • 24S-Hydroxycholesterol enhances synaptic vesicle cycling in the mouse neuromuscular junction: Implication of glutamate NMDA receptors and nitric oxide.

    abstract::24S-hydroxycholesterol (24S-HC) is a brain-derived product of lipid metabolism present in the systemic circulation, where its level can change significantly in response to physiological and pathophysiological conditions. Here, using electrophysiological and optical approaches, we have found a high sensitivity to 24S-H...


    pub_type: 杂志文章


    authors: Kasimov MR,Fatkhrakhmanova MR,Mukhutdinova KA,Petrov AM

    更新日期:2017-05-01 00:00:00

  • The new antiepileptic drugs lamotrigine and felbamate are effective in phenytoin-resistant kindled rats.

    abstract::We evaluated the anticonvulsant efficacy of the antiepileptic drugs (AEDs) lamotrigine (LTG) and felbamate (FBM) in amygdala kindled rats that had been preselected with respect to their response to phenytoin. Anticonvulsant response was tested by determining the afterdischarge threshold (ADT), i.e., a sensitive measur...


    pub_type: 杂志文章


    authors: Ebert U,Reissmüller E,Löscher W

    更新日期:2000-07-24 00:00:00

  • Moclobemide reduces intracellular pH and neuronal activity of CA3 neurones in guinea-pig hippocampal slices-implication for its neuroprotective properties.

    abstract::Mechanisms underlying the neuroprotective properties of the weak MAO-A inhibitor moclobemide are not understood. Increasing evidence suggests that a moderate increase in intracellular free protons may contribute to neuroprotective properties due to a proton-mediated decrease in neuronal activity. Therefore, we studied...


    pub_type: 杂志文章


    authors: Bonnet U,Leniger T,Wiemann M

    更新日期:2000-08-23 00:00:00

  • Novel sulfoglycolipid IG20 causes neuroprotection by activating the phase II antioxidant response in rat hippocampal slices.

    abstract::Compound IG20 is a newly synthesised sulphated glycolipid that promotes neuritic outgrowth and myelinisation, at the time it causes the inhibition of glial proliferation and facilitates exocytosis in chromaffin cells. Here we have shown that IG20 at 0.3-10 μM afforded neuroprotection in rat hippocampal slices stressed...


    pub_type: 杂志文章


    authors: Punzón E,García-Alvarado F,Maroto M,Fernández-Mendívil C,Michalska P,García-Álvarez I,Arranz-Tagarro JA,Buendia I,López MG,León R,Gandía L,Fernández-Mayoralas A,García AG

    更新日期:2017-04-01 00:00:00

  • Therapeutic strategies to target acute and long-term sequelae of pediatric traumatic brain injury.

    abstract::Pediatric traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality in children. Experimental and clinical studies demonstrate that the developmental age, the type of injury (diffuse vs. focal) and sex may play important roles in the response of the developing brain to a traumatic injur...


    pub_type: 杂志文章,评审


    authors: Huh JW,Raghupathi R

    更新日期:2019-02-01 00:00:00

  • Ciclopirox prevents peroxynitrite toxicity in astrocytes by maintaining their mitochondrial function: a novel mechanism for cytoprotection by ciclopirox.

    abstract::Previously we have reported that astrocytes deprived of glucose were highly vulnerable to peroxynitrite (Choi and Kim, J. Neurosci. Res. 54 (1998) 870; Neurosci. Lett. 256 (1988) 109; Ju et al., J. Neurochem. 74 (2000) 1989). Here we report that ciclopirox, which is clinically used as an anti-fungal agent, completely ...


    pub_type: 杂志文章


    authors: Choi JJ,Kong MY,Lee SJ,Kim HC,Ko KH,Kim WK

    更新日期:2002-09-01 00:00:00

  • (3-Aminocyclopentyl)methylphosphinic acids: novel GABA(C) receptor antagonists.

    abstract::Our understanding of the role GABA(C) receptors play in the central nervous system is limited due to a lack of specific ligands. Here we describe the pharmacological effects of (+/-)-cis-3- and (+/-)-trans-3-(aminocyclopentyl)methylphosphinic acids ((+/-)-cis- and (+/-)-trans-3-ACPMPA) as novel ligands for the GABA(C)...


    pub_type: 杂志文章


    authors: Chebib M,Hanrahan JR,Kumar RJ,Mewett KN,Morriss G,Wooller S,Johnston GA

    更新日期:2007-03-01 00:00:00

  • Cholecystokinin octapeptide, caerulein and caerulein analogues: effects on thermoregulation in the mouse.

    abstract::Cholecystokinin octapeptide (CCK-8), caerulein and seven out of ten analogues of caerulein produced in mice, after subcutaneous administration, a dose-dependent drop in rectal temperature. For the hypothermic effect, i.e. a decrease in temperature by at least 1.5 degree C, ED50's were estimated with these peptides and...


    pub_type: 杂志文章


    authors: Zetler G

    更新日期:1982-08-01 00:00:00

  • Oxytocin inhibits the rat medullary dorsal horn Sp5c/C1 nociceptive transmission through OT but not V1A receptors.

    abstract::The medullary dorsal horn (MDH or Sp5c/C1 region) plays a key role modulating the nociceptive input arriving from craniofacial structures. Some reports suggest that oxytocin could play a role modulating the nociceptive input at the MDH level, but no study has properly tested this hypothesis. Using an electrophysiologi...


    pub_type: 杂志文章


    authors: García-Boll E,Martínez-Lorenzana G,Condés-Lara M,González-Hernández A

    更新日期:2018-02-01 00:00:00

  • Warmer preparation of hippocampal slices prevents synapse proliferation that might obscure LTP-related structural plasticity.

    abstract::The hippocampal slice is a popular model system in which to study the cellular properties of long-term potentiation (LTP). Synaptogenesis induced by exposure to ice-cold artificial cerebrospinal fluid (ACSF), however, raises the concern that morphological correlates of LTP might be obscured, especially in mature slice...


    pub_type: 杂志文章


    authors: Bourne JN,Kirov SA,Sorra KE,Harris KM

    更新日期:2007-01-01 00:00:00

  • Selective potentiating effect of beta-p-chlorophenylglutamate on responses induced by certain sulphur-containing excitatory amino acids and quisqualate.

    abstract::In dorsal horn neurones of the cat spinal cord iontophoretically administered (+/-)-beta-p-chlorophenylglutamate (chlorpheg) markedly enhanced the excitatory responses induced by L-homocysteate, L-homocysteine sulphinate, S-sulpho L-cysteine, L-cysteate and quisqualate, while responses to NMDA, kainate, L-glutamate, L...


    pub_type: 杂志文章


    authors: Davies J,Francis AA,Oakes DJ,Sheardown MJ,Watkins JC

    更新日期:1985-02-01 00:00:00

  • Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain.

    abstract::Diabetic neuropathic pain remains an unmet clinical problem and is poorly relieved by conventional analgesics. N-methyl-D-aspartate (NMDA) receptors play an important role in central sensitization in neuropathic pain. Although NMDA antagonists are highly effective in reducing neuropathic pain, these agents cause sever...


    pub_type: 杂志文章


    authors: Chen SR,Samoriski G,Pan HL

    更新日期:2009-08-01 00:00:00

  • The effects of adrenalectomy and ovariectomy on the behavioral and hypothermic responses of rats to 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT).

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    pub_type: 杂志文章


    authors: Young AH,Dow RC,Goodwin GM,Fink G

    更新日期:1993-07-01 00:00:00

  • T1-11 and JMF1907 ameliorate polyglutamine-expanded ataxin-3-induced neurodegeneration, transcriptional dysregulation and ataxic symptom in the SCA3 transgenic mouse.

    abstract::More studies are required to develop therapeutic agents for treating spinocerebellar ataxia type 3 (SCA3), which is caused by mutant polyglutamine-expanded ataxin-3 and is the most prevalent subtype of spinocerebellar ataxias. T1-11 [N6-(4-Hydroxybenzyl) adenosine], isolated from a Chinese medicinal herb Gastordia ela...


    pub_type: 杂志文章


    authors: Chou AH,Chen YL,Chiu CC,Yuan SJ,Weng YH,Yeh TH,Lin YL,Fang JM,Wang HL

    更新日期:2015-12-01 00:00:00

  • Studies on the pharmacology of central opioid-induced increases in plasma catecholamines in conscious rats.

    abstract::Centrally-administered opioid peptides produce elevations in levels of catecholamines in plasma in conscious rats. To investigate the opioid receptor involved in mediating this response, morphine (3.5-105 nmol), [D-Ala2-D-Leu5]enkephalin (DADL, 1.05-35 nmol) and U50, 488H (35-1160 nmol), relatively selective ligands f...


    pub_type: 杂志文章


    authors: Conway EL,Brown MJ,Dollery CT

    更新日期:1984-11-01 00:00:00

  • Prioritizing the development of mouse models for childhood brain disorders.

    abstract::Mutations in hundreds of genes contribute to cognitive and behavioral dysfunction associated with developmental brain disorders (DBDs). Due to the sheer number of risk factors available for study combined with the cost of developing new animal models, it remains an open question how genes should be prioritized for in-...


    pub_type: 杂志文章,评审


    authors: Ogden KK,Ozkan ED,Rumbaugh G

    更新日期:2016-01-01 00:00:00

  • Vaccine blunts fentanyl potency in male rhesus monkeys.

    abstract::One proposed factor contributing to the increased frequency of opioid overdose deaths is the emergence of novel synthetic opioids, including illicit fentanyl and fentanyl analogues. A treatment strategy currently under development to address the ongoing opioid crisis is immunopharmacotherapies or opioid-targeted vacci...


    pub_type: 杂志文章


    authors: Tenney RD,Blake S,Bremer PT,Zhou B,Hwang CS,Poklis JL,Janda KD,Banks ML

    更新日期:2019-11-01 00:00:00

  • Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by alpha-adrenergic receptor antagonists.

    abstract::Effects of clonidine and tizanidine, which have antinociceptive and alpha 2-agonistic actions, were studied on the release of substance P from slices of spinal cord from the rat. Veratridine-evoked depolarization induced a 2-3-fold increase in the release of substance P from the slices of spinal cord. Exposure of the ...


    pub_type: 杂志文章


    authors: Ono H,Mishima A,Ono S,Fukuda H,Vasko MR

    更新日期:1991-06-01 00:00:00

  • Block of calcium channels in rat neurons by synthetic omega-Aga-IVA.

    abstract::We investigated block of voltage-dependent Ca channels in freshly dissociated rat central and peripheral neurons by the synthetic peptide omega-Aga-IVA. Synthetic omega-Aga-IVA blocked approximately 90% of the high-threshold Ca current in cerebellar Purkinje neurons with an estimated Kd of approximately 1.5 nM, slight...


    pub_type: 杂志文章


    authors: Mintz IM,Bean BP

    更新日期:1993-11-01 00:00:00

  • Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors.

    abstract::The mechanisms underlying the neuroprotective effects of cannabidiol (CBD) were studied in vivo using a hypoxic-ischemic (HI) brain injury model in newborn pigs. One- to two-day-old piglets were exposed to HI for 30 min by interrupting carotid blood flow and reducing the fraction of inspired oxygen to 10%. Thirty minu...


    pub_type: 杂志文章


    authors: Pazos MR,Mohammed N,Lafuente H,Santos M,Martínez-Pinilla E,Moreno E,Valdizan E,Romero J,Pazos A,Franco R,Hillard CJ,Alvarez FJ,Martínez-Orgado J

    更新日期:2013-08-01 00:00:00

  • NMDA receptors in nervous system diseases.

    abstract::NMDA receptor (NMDAR) dysfunction has emerged as a common theme in several major nervous system disorders, including ischemic brain injury, chronic neurodegenerative diseases, pain, depression and schizophrenia. Either hyperactivity or hypofunction of NMDARs could contribute to disease pathophysiology. It is likely th...


    pub_type: 杂志文章,评审


    authors: Zhou Q,Sheng M

    更新日期:2013-11-01 00:00:00

  • Alcohols inhibit N-methyl-D-aspartate receptors via a site exposed to the extracellular environment.

    abstract::N-Methyl-D-aspartate (NMDA) receptors are important CNS target sites of alcohols, but the site and mechanism of action of alcohols on NMDA receptors remains unclear. In CHO-K1 cells transfected with NR1/NR2B NMDA receptor subunits, ethanol inhibited NMDA-activated current with an IC(50) of 138 mM. Truncation of the in...


    pub_type: 杂志文章


    authors: Peoples RW,Stewart RR

    更新日期:2000-07-24 00:00:00

  • Regulation of GIRK channel deactivation by Galpha(q) and Galpha(i/o) pathways.

    abstract::G protein regulated inward rectifying potassium channels (GIRKs) are activated by G protein coupled receptors (GPCRs) via the G protein betagamma subunits. However, little is known about the effects of different GPCRs on the deactivation kinetics of transmitter-mediated GIRK currents. In the present study we investiga...


    pub_type: 杂志文章


    authors: Mark MD,Ruppersberg JP,Herlitze S

    更新日期:2000-09-01 00:00:00

  • Prior stimulation of the endocannabinoid system prevents methamphetamine-induced dopaminergic neurotoxicity in the striatum through activation of CB2 receptors.

    abstract::Methamphetamine toxicity is associated with cell death and loss of dopamine neuron terminals in the striatum similar to what is found in some neurodegenerative diseases. Conversely, the endocannabinoid system (ECS) has been suggested to be neuroprotective in the brain, and new pharmacological tools have been developed...


    pub_type: 杂志文章


    authors: Nader J,Rapino C,Gennequin B,Chavant F,Francheteau M,Makriyannis A,Duranti A,Maccarrone M,Solinas M,Thiriet N

    更新日期:2014-12-01 00:00:00

  • Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice.

    abstract::Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory deficits and cognitive decline. Amyloid-β (Aβ) deposition and cholinergic defect are widely thought to be the underlying mechanism of learning and memory impairment. Geniposide, which is the main active component of the tradit...


    pub_type: 杂志文章


    authors: Zhao C,Zhang H,Li H,Lv C,Liu X,Li Z,Xin W,Wang Y,Zhang W

    更新日期:2017-04-01 00:00:00

  • First-in-class thyrotropin-releasing hormone (TRH)-based compound binds to a pharmacologically distinct TRH receptor subtype in human brain and is effective in neurodegenerative models.

    abstract::JAK4D, a first-in-class thyrotropin-releasing hormone (TRH)-based compound, is a prospective therapeutic candidate offering a multifaceted approach to treating neurodegeneration and other CNS conditions. The purpose of these studies was to determine the ability of JAK4D to bind to TRH receptors in human brain and to e...


    pub_type: 杂志文章


    authors: Kelly JA,Boyle NT,Cole N,Slator GR,Colivicchi MA,Stefanini C,Gobbo OL,Scalabrino GA,Ryan SM,Elamin M,Walsh C,Vajda A,Goggin MM,Campbell M,Mash DC,O'Mara SM,Brayden DJ,Callanan JJ,Tipton KF,Della Corte L,Hunter J,

    更新日期:2015-02-01 00:00:00

  • Stress-induced activation of the brainstem Bcl-xL gene expression in rats treated with fluoxetine: correlations with serotonin metabolism and depressive-like behavior.

    abstract::Mechanisms underlying stress-induced depression and antidepressant drug action were shown to involve alterations in serotonergic (5-HT) neurotransmission and expression of genes coding for proteins associated with neurotrophic signaling pathways and cell-survival in the hippocampus and cortex. Expression of these gene...


    pub_type: 杂志文章


    authors: Shishkina GT,Kalinina TS,Berezova IV,Dygalo NN

    更新日期:2012-01-01 00:00:00

  • Noradrenergic control of the bed nucleus of the stria terminalis in stress and reward.

    abstract::The bed nucleus of the stria terminalis (BNST) is a group of inter-connected subnuclei that play critical roles in stress-reward interactions. An interesting feature of this brain region is the massive noradrenergic input that it receives. Important roles for norepinephrine in this region have been documented in a num...


    pub_type: 杂志文章,评审


    authors: Flavin SA,Winder DG

    更新日期:2013-07-01 00:00:00