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Brisa García-Vilchis, Paola Suárez, Miguel Serrano-Reyes, Mario Arias-García, Dagoberto Tapia, Mariana Duhne, José Bargas, Elvira Galarraga
Different corticostriatal suprathreshold responses in direct and indirect striatal projection neurons (SPNs) of rodents have been reported. Responses consist in prolonged synaptic potentials of polysynaptic and intrinsic origin, in which voltage-gated Ca²⁺-currents play a role. Recording simultaneous Ca²⁺-imaging and voltage responses at the soma, while activating the corticostriatal pathway, we show that encoding of synaptic responses into trains of action potentials (APs) is different in SPNs: firing of APs in D1-SPNs increase gradually, in parallel with Ca²⁺-entry, as a function of stimulus intensity...
November 12, 2018: Synapse
Steven Vetel, Sophie Sérrière, Johnny Vercouillie, Jackie Vergote, Gabrielle Chicheri, Jean-Bernard Deloye, Frédéric Dollé, Sylvie Bodard, Claire Tronel, Lydie Nadal-Desbarats, Antoine Lefèvre, Patrick Emond, Sylvie Chalon
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons constituting the nigrostriatal pathway. Neuroinflammation, related to microglial activation, plays an important role in this process. Exploration of animal models of PD using neuroimaging modalities allows to better understand the pathophysiology of the disease. Here, we fully explored a moderate lesion model in the rat in which 6-hydroxydopamine was unilaterally delivered in three sites along the striatum. The degenerative process was assessed through in vivo Positron Emission Tomography (PET) imaging and in vitro autoradiographic quantitation of the striatal dopamine transporter (DAT) and immunostaining of tyrosine hydroxylase (TH)...
October 28, 2018: Synapse
Yi Chang, Hsi Lung Hsieh, Shu Kuei Huang, Su Jane Wang
Allopregnanolone, an active metabolite of progesterone, has been reported to exhibit neuroprotective activity in several preclinical models. Considering that the excitotoxicity caused by excessive glutamate is implicated in many brain disorders, the effect of allopregnanolone on glutamate release in rat cerebrocortical nerve terminals and possible underlying mechanism were investigated. We observed that allopregnanolone inhibited 4-aminopyridine (4-AP)-evoked glutamate release, and this inhibition was prevented by chelating the extracellular Ca2+ ions and the vesicular transporter inhibitor...
October 25, 2018: Synapse
Rajamani Selvam, Mason L Yeh, Eric S Levine
Brain-derived neurotrophic factor (BDNF), traditionally known for promoting neuronal growth and development, is also a modulator of synaptic transmission. In addition to the well-characterized effects at excitatory synapses, BDNF has been shown to acutely suppress inhibitory neurotransmission; however, the underlying mechanisms are unclear. We have previously shown that at inhibitory synapses in layer 2/3 of the somatosensory cortex, BDNF induces the mobilization of endogenous cannabinoids (eCBs) that act retrogradely to suppress GABA release...
October 17, 2018: Synapse
Zade R Holloway, Timothy G Freels, Josiah F Comstock, Hunter G Nolen, Helen J Sable, Deranda B Lester
Midbrain dopaminergic neurons project to and modulate multiple highly interconnected modules of the basal ganglia, limbic system, and frontal cortex. Dopamine regulates behaviors associated with action selection in the striatum, reward in the nucleus accumbens (NAc), emotional processing in the amygdala, and executive functioning in the medial prefrontal cortex (mPFC). The multifunctionality of dopamine likely occurs at the individual synapses, with varied levels of phasic dopamine release acting on different receptor populations...
October 13, 2018: Synapse
Aiyana D Batton, Charles D Blaha, Allan Bieber, Kendall H Lee, Suelen L Boschen
Although dopamine is commonly studied for its role in incentive-motivation, cognition, and various neuropsychiatric disorders, evidence from Parkinson's disease patients that present auditory deficits suggest that dopamine is also involved in central auditory processing. It has been recently discovered that the subparafascicular thalamic nucleus (SPF) sends dopaminergic projections to the inferior colliculus (IC), an important convergence hub for the ascending and descending auditory pathways. In the present study, our aim was to provide neurochemical evidence that activation of SPF neurons evokes dopamine release in the IC of anesthetized rats using fast-scan cyclic and paired pulse voltammetry in combination with carbon fiber microelectrodes...
October 6, 2018: Synapse
Jiaxian Zhang, Yu Jing, Hu Zhang, David K Bilkey, Ping Liu
Microglia, the resident immune cells in the central nervous system, play critical roles in neurodevelopment, synaptic pruning and neuronal wiring. Early in development, microglia migrate via the tangential and radial migration pathways to their final destinations and mature gradually, a process that includes morphological changes. Recent research has implicated microglial abnormality in the etiology of schizophrenia. Since prenatal exposure to viral or bacterial infections due to maternal immune activation (MIA) leads to increased risk of schizophrenia in offspring during adulthood, the present study systematically investigated how MIA induced by polyinosinic:polycytidilic acid (a mimic of viral double stranded RNA) affected microglial immunoreactivity along the migration and maturation trajectories in the brains of male and female rat offspring at postnatal day (PND) 2...
September 26, 2018: Synapse
Timothy D Folsom, LeeAnn Higgins, Todd W Markowski, Timothy J Griffin, S Hossein Fatemi
The fragile X mental retardation 1 knockout (Fmr1 KO) mouse replicates behavioral deficits associated with autism, fragile X syndrome, and schizophrenia. Less is known whether protein expression changes are consistent with findings in subjects with schizophrenia. In the current study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics to determine the protein expression of four subcellular fractions in the forebrains of Fmr1 KO mice vs. C57BL/6 J mice and the effect of a negative allosteric modulator of mGluR5-2-Methyl-6-(phenylethynyl)pyridine (MPEP)-on protein expression...
September 3, 2018: Synapse
Savannah Tollefson, Joshua Gertler, Michael L Himes, Jennifer Paris, Steve Kendro, Brian Lopresti, N Scott Mason, Rajesh Narendran
Phosphodiesterase-10a (PDE10a) is located exclusively in medium spiny neurons (MSN). Rodent studies show an increase in striatal MSN spine density following exposure to cocaine. These increases in MSN spine density are suggested to underlie neurobiological changes which contribute to cocaine self-administration. No postmortem or imaging studies have confirmed this finding in humans. Here, we hypothesized an increase in the MSN marker PDE10a in subjects with cocaine use disorder ("cocaine users") compared to controls...
January 2019: Synapse
Mahendra Singh, Brendan Lujan, Robert Renden
Synaptic vesicle (SV) exocytosis is intimately dependent on free local Ca2+ near active zones. Genetically encoded calcium indicators (GECIs) have become an indispensable tool to monitor calcium dynamics during physiological responses, and they are widely used as a proxy to monitor activity in neuronal ensembles and at synaptic terminals. However, GECIs' ability to bind Ca2+ at physiologically relevant concentration makes them strong candidates to affect calcium homeostasis and alter synaptic transmission by exogenously increasing Ca2+ buffering...
December 2018: Synapse
Rodolfo Sánchez-Zavaleta, Hernán Cortés, José Arturo Avalos-Fuentes, Ubaldo García, José Segovia Vila, David Erlij, Benjamín Florán
Recent studies suggested the expression of CB2 receptors in neurons of the CNS, however, most of these studies have only explored one aspect of the receptors, i.e., expression of protein, messenger RNA, or functional response, and more complete studies appear to be needed to establish adequately their role in the neuronal function. Electron microscopy studies showed the presence of CB2r in asymmetric terminals of the substantia nigra pars reticulata (SNr), and its mRNA appeared is expressed in the subthalamic nucleus...
November 2018: Synapse
Anne E Homan, Stephen D Meriney
The impact of presynaptic transmitter release site organization on synaptic function has been a vibrant area of research for synaptic physiologists. Because there is a highly nonlinear relationship between presynaptic calcium influx and subsequent neurotransmitter release at synapses, the organization and density of calcium sources (voltage-gated calcium channels [VGCCs]) relative to calcium sensors located on synaptic vesicles is predicted to play a major role in shaping the dynamics of neurotransmitter release at a synapse...
November 2018: Synapse
Kelly Smart, Sylvia M L Cox, Atsuko Nagano-Saito, Pedro Rosa-Neto, Marco Leyton, Chawki Benkelfat
[11 C]ABP688 is a positron emission tomography (PET) radioligand that binds selectively to metabotropic glutamate type 5 receptors (mGluR5). The use of this tracer has identified receptor binding changes in clinical populations, and has been informative in drug occupancy studies. However, previous studies have found significant increases in [11 C]ABP688 binding in the later scan of same-day comparisons, and estimates of test-retest reliability under consistent scanning conditions are not available. The objective of this study was to assess the variability of [11 C]ABP688 binding in healthy people in scans performed at the same time of day...
September 2018: Synapse
Jeffrey M Miller, Francesca Zanderigo, Priya D Purushothaman, Christine DeLorenzo, Harry Rubin-Falcone, R Todd Ogden, John Keilp, Maria A Oquendo, Nabeel Nabulsi, Yiyun H Huang, Ramin V Parsey, Richard E Carson, J John Mann
Endogenous kappa opioids mediate pathological responses to stress in animal models. However, the relationship of the kappa opioid receptor (KOR) to life stress and to psychopathology in humans is not well described. This pilot study sought, for the first time, to quantify KOR in major depressive disorder (MDD) in vivo in humans using positron emission tomography (PET). KOR binding was quantified in vivo by PET imaging with the [11 C]GR103545 radiotracer in 13 healthy volunteers and 10 participants with current MDD...
September 2018: Synapse
Joshua Gertler, Savannah Tollefson, Rehima Jordan, Michael L Himes, N Scott Mason, W Gordon Frankle, Rajesh Narendran
Studies in nonhuman primates and humans have demonstrated that amphetamine-induced dopamine release in the cortex can be measured with [11 C]FLB 457 and PET imaging. This technique has been successfully used in recent clinical studies to show decreased dopamine transmission in the prefrontal cortex in schizophrenia and alcohol dependence. Here, we present data from a cohort of twelve healthy controls in whom an oral amphetamine challenge (0.5 mg kg-1 ) did not lead to a significant reduction in [11 C]FLB 457 BPND (i...
September 2018: Synapse
Ayako Kumagai, Tsutomu Sasaki, Kenta Matsuoka, Masayoshi Abe, Toshihide Tabata, Yumi Itoh, Hiroyuki Fuchino, Sartagul Wugangerile, Mika Suga, Tomoko Yamaguchi, Hidehisa Kawahara, Yasuo Nagaoka, Kenji Kawabata, Miho Kusuda Furue, Hiroshi Takemori
Dysfunction of mitochondrial activity is often associated with the onset and progress of neurodegenerative diseases. Membrane depolarization induced by Na+ influx increases intracellular Ca2+ levels in neurons, which upregulates mitochondrial activity. However, overlimit of Na+ influx and its prolonged retention ultimately cause excitotoxicity leading to neuronal cell death. To return the membrane potential to the normal level, Na+ /K+ -ATPase exchanges intracellular Na+ with extracellular K+ by consuming a large amount of ATP...
August 18, 2018: Synapse
Cesar Pinzón-Parra, Blanca Vidal-Jiménez, Israel Camacho-Abrego, Alejandra A Flores-Gómez, Antonio Rodríguez-Moreno, Gonzalo Flores
Little has been investigated about the effects of stress on synaptic communication at prepubertal age, a stage considered as juvenile. This period of development is related to socialization through play. Our group has studied the changes of neuronal morphology in limbic structures caused by stress at prenatal and at early postnatal ages (before weaning) in the rat. In the present study, we assessed the effect of restraint stress at juvenile ages. Male Sprague-Dawley rats from postnatal day (PD) 21 to PD35 were restrained (from movement) for 2 hrs...
August 13, 2018: Synapse
Elizabeth Monserrat Hernández-Hernández, Karen Caporal Hernandez, Rubén Antonio Vázquez-Roque, Alfonso Díaz, Fidel de la Cruz, Benjamin Florán, Gonzalo Flores
Aging is a stage of life where cognitive and motor functions are impaired. This is because oxidative and inflammatory processes exacerbate neurodegeneration, which affects dendritic morphology and neuronal communication of limbic regions with memory loss. Recently, the use of trophic substances has been proposed to prevent neuronal deterioration. The neuropeptide-12 (N-PEP-12) has been evaluated in elderly patients with dementia, showing improvements in cognitive tasks due to acts as a neurotrophic factor. In the present work, we evaluated the effect of N-PEP-12 on motor activity and recognition memory, as well as its effects on dendritic morphology and the immunoreactivity of GFAP, Synaptophysin (SYP), and BDNF in neurons of the prefrontal cortex (PFC), dorsal hippocampus (DH) and nucleus accumbens (NAcc) of aged rats...
August 2018: Synapse
Onarae V Rice, Charles R Ashby, Clark Dixon, William Laurenzo, Jason Hayden, Rui Song, Jin Li, Amit K Tiwari, Eliot L Gardner
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric syndrome that occurs in individuals exposed to extremely threatening or traumatic events. In both animals and humans, dopamine (DA) function appears to be dysregulated in brain areas involved in the conditioned fear response(s) that underlie PTSD. In this study, we determined the effect of the selective DA D3 receptor antagonists YQA14A (6.25, 12.5 and 25 mg/kg i.p.) and SB-277011A (6 mg/kg i.p.) on tone-induced fear (assessed by measuring freeze time) in a modified version of the single-prolonged stress (SPS) model of PTSD in adult male Sprague-Dawley rats...
August 2018: Synapse
Vassilios Papaleonidopoulos, Stylianos Kouvaros, Costas Papatheodoropoulos
Hippocampus is importantly involved in dopamine-dependent behaviors and dopamine is a significant modulator of synaptic plasticity in the hippocampus. Moreover, the dopaminergic innervation appears to be disproportionally segregated along the hippocampal longitudinal (dorsoventral) axis with unknown consequences for synaptic plasticity. In this study we examined the actions of endogenously released dopamine and the effects of exogenous D1/D5 dopamine receptor agonists on theta-burst stimulation-induced long-term potentiation (LTP) of field excitatory synaptic potential (fEPSP) at Schaffer collateral-CA1 synapses in slices from dorsal (DH) and ventral hippocampus (VH)...
August 2018: Synapse
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