Postnatal development of excitatory postsynaptic currents in nucleus accumbens medium spiny neurons

Neuroscience ◽  
2008 ◽  
Vol 154 (4) ◽  
pp. 1440-1449 ◽  
Author(s):  
L. Zhang ◽  
R.A. Warren
Keyword(s):  
Nucleus Accumbens ◽  
Postnatal Development ◽  
Medium Spiny Neurons ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Spiny Neurons

scholarly journals Dopaminergic Modulation of Excitatory Postsynaptic Currents in Rat Neostriatal Neurons

1997 ◽  
Vol 78 (3) ◽  
pp. 1248-1255 ◽  
Author(s):  
Masashi Umemiya ◽  
Lynn A. Raymond
Keyword(s):  
Dopamine Receptor ◽  
Glutamate Receptor ◽  
Skf 38393 ◽  
Medium Spiny Neuron ◽  
Medium Spiny Neurons ◽  
Excitatory Postsynaptic Currents ◽  
Epsc Amplitude ◽  
Postsynaptic Currents ◽  
Spiny Neurons ◽  
Dopaminergic Modulation

Umemiya, Masashi and Lynn A. Raymond. Dopaminergic modulation of excitatory postsynaptic currents in rat neostriatal neurons. J. Neurophysiol. 78: 1248–1255, 1997. γ-aminobutyric acid (GABA)-containing medium spiny neurons constitute ∼90% of the neuronal population in the neostriatum (caudate and putamen) and play an important role in motor programming. Cortical glutamatergic afferents provide the main excitatory drive for these neurons, whereas nigral dopaminergic neurons play a crucial role in regulating their activity. To further investigate the mechanisms underlying the dopaminergic modulation of medium spiny neuronal activity, we tested the effect of dopamine receptor agonists on excitatory synaptic transmission recorded from these neurons. Excitatory postsynaptic currents (EPSCs) were evoked by local stimulation and recorded from medium spiny neurons in postnatal rat striatal thin brain slices. Recordings were made using the whole cell patch-clamp technique under voltage clamp and conditions that selected for the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate- and kainate-type glutamate receptor-mediated components of the EPSC. Incubation of slices in 10 μM dopamine resulted in a 33 ± 11% (mean ± SE) decrease in the amplitude of evoked EPSCs, an effect that developed during seconds. The relative variability in amplitude of dopamine's effects on medium spiny neuron EPSCs may reflect activation of different receptor subtypes with opposing effects. In contrast to the results with dopamine, incubation of slices in SKF 38393, a D1-type dopamine receptor selective agonist, resulted in dose-dependent potentiation of the medium spiny neuron EPSC that developed during several minutes. At a concentration of 5 μM, SKF 38393 resulted in a 29 ± 4.5% increase in EPSC amplitude, an effect that was blocked by preincubation with the D1-selective antagonist, SCH 23390 (10 μM). On the other hand, 5 μM SKF 38393 had no apparent effect on medium spiny neuron currents activated by exogenous application of glutamate or kainate. However, because of the inherent limitations of rapid agonist perfusion in the brain slice preparation (caused by slow agonist diffusion and rapid glutamate receptor desensitization) and because of anatomic evidence that colocalizes D1 and glutamate receptors to medium spiny neuron dendrites, our results leave open the possibility that the effect of D1 receptor activation on the EPSC is mediated via modulation of postsynaptic glutamate receptor responsiveness. The significant potentiation by D1 receptor agonists of EPSC amplitude at the cortico-striatal medium spiny synapse that we observed, in part, may underlie the role of D1 receptors in facilitating medium spiny neuronal firing, with implications for understanding regulation of movement.

scholarly journals Selective filtering of excitatory inputs to nucleus accumbens by dopamine and serotonin

2021 ◽  
Vol 118 (24) ◽  
pp. e2106648118
Author(s):  
Daniel J. Christoffel ◽  
Jessica J. Walsh ◽  
Paul Hoerbelt ◽  
Boris D. Heifets ◽  
Pierre Llorach ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Basolateral Amygdala ◽  
Behavioral Effects ◽  
Medium Spiny Neurons ◽  
Excitatory Postsynaptic Currents ◽  
Spiny Neurons ◽  
Specific Manner ◽  
Paraventricular Thalamus ◽  
Motivated Behaviors ◽  
Synaptic Effects

The detailed mechanisms by which dopamine (DA) and serotonin (5-HT) act in the nucleus accumbens (NAc) to influence motivated behaviors in distinct ways remain largely unknown. Here, we examined whether DA and 5-HT selectively modulate excitatory synaptic transmission in NAc medium spiny neurons in an input-specific manner. DA reduced excitatory postsynaptic currents (EPSCs) generated by paraventricular thalamus (PVT) inputs but not by ventral hippocampus (vHip), basolateral amygdala (BLA), or medial prefrontal cortex (mPFC) inputs. In contrast, 5-HT reduced EPSCs generated by inputs from all areas except the mPFC. Release of endogenous DA and 5-HT by methamphetamine (METH) and (±)3,4-methylenedioxymethamphetamine (MDMA), respectively, recapitulated these input-specific synaptic effects. Optogenetic inhibition of PVT inputs enhanced cocaine-conditioned place preference, whereas mPFC input inhibition reduced the enhancement of sociability elicited by MDMA. These findings suggest that the distinct, input-specific filtering of excitatory inputs in the NAc by DA and 5-HT contribute to their discrete behavioral effects.

Different Inhibitory Inputs Onto Neostriatal Projection Neurons as Revealed by Field Stimulation

2005 ◽  
Vol 93 (2) ◽  
pp. 1119-1126 ◽  
Author(s):  
Fatuel Tecuapetla ◽  
Luis Carrillo-Reid ◽  
Jaime N. Guzmán ◽  
Elvira Galarraga ◽  
José Bargas
Keyword(s):  
Channel Blocker ◽  
Inhibitory Synapses ◽  
Projection Neurons ◽  
Medium Spiny Neurons ◽  
Field Stimulation ◽  
Paired Pulse ◽  
Postsynaptic Currents ◽  
Spiny Neurons ◽  
Short Time ◽  
Paired Pulse Depression

This work investigated if diverse properties could be ascribed to evoked inhibitory postsynaptic currents (IPSCs) recorded on rat neostriatal neurons when field stimulation was delivered at two different locations: the globus pallidus (GP) and the neostriatum (NS). Previous work stated that stimulation in the GP could antidromically excite projection axons from medium spiny neurons. This maneuver would predominantly activate the inhibitory synapses that interconnect spiny cells. In contrast, intrastriatal stimulation would preferentially activate inhibitory synapses provided by interneurons. This study shows that, in fact, intensity-amplitude experiments are able to reveal different properties for IPSCs evoked from these two locations (GP and NS). In addition, while all IPSCs evoked from the GP were always sensitive to ω-conotoxin GVIA (CaV2.22.2 or N-channel blocker), one-half of the inhibition evoked from the NS exhibited little sensitivity to ω-conotoxin GVIA. Characteristically, all ω-conotoxin GVIA–insensitive IPSCs exhibited strong paired pulse depression, whereas ω-conotoxin GVIA–sensitive IPSCs evoked from either the GP or the NS could exhibit short-time depression or facilitation. ω-Agatoxin TK (CaV2.12.1+ or P/Q-channel blocker) blocked IPSCs evoked from both locations. Therefore 1) distinct inhibitory inputs onto projection neostriatal cells can be differentially stimulated with field electrodes; 2) N-type Ca2+ channels are not equally expressed in inhibitory terminals activated in the NS; and 3) synapses that interconnect spiny neurons use both N- and P/Q-type Ca2+ channels.

scholarly journals Microglial NFκB-TNFα hyperactivation induces obsessive–compulsive behavior in mouse models of progranulin-deficient frontotemporal dementia

2017 ◽  
Vol 114 (19) ◽  
pp. 5029-5034 ◽  
Author(s):  
Grietje Krabbe ◽  
S. Sakura Minami ◽  
Jon I. Etchegaray ◽  
Praveen Taneja ◽  
Biljana Djukic ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Frontotemporal Dementia ◽  
Knockout Mice ◽  
Nuclear Factor Κb ◽  
Medium Spiny Neurons ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Spiny Neurons ◽  
Increased Risk ◽  
Excessive Grooming

Frontotemporal dementia (FTD) is the second most common dementia before 65 years of age. Haploinsufficiency in the progranulin (GRN) gene accounts for 10% of all cases of familial FTD. GRN mutation carriers have an increased risk of autoimmune disorders, accompanied by elevated levels of tissue necrosis factor (TNF) α. We examined behavioral alterations related to obsessive–compulsive disorder (OCD) and the role of TNFα and related signaling pathways in FTD patients with GRN mutations and in mice lacking progranulin (PGRN). We found that patients and mice with GRN mutations displayed OCD and self-grooming (an OCD-like behavior in mice), respectively. Furthermore, medium spiny neurons in the nucleus accumbens, an area implicated in development of OCD, display hyperexcitability in PGRN knockout mice. Reducing levels of TNFα in PGRN knockout mice abolished excessive self-grooming and the associated hyperexcitability of medium spiny neurons of the nucleus accumbens. In the brain, PGRN is highly expressed in microglia, which are a major source of TNFα. We therefore deleted PGRN specifically in microglia and found that it was sufficient to induce excessive grooming. Importantly, excessive grooming in these mice was prevented by inactivating nuclear factor κB (NF-κB) in microglia/myeloid cells. Our findings suggest that PGRN deficiency leads to excessive NF-κB activation in microglia and elevated TNFα signaling, which in turn lead to hyperexcitability of medium spiny neurons and OCD-like behavior.

scholarly journals Sex-Specific Role for Egr3 in Nucleus Accumbens D2-Medium Spiny Neurons Following Long-Term Abstinence From Cocaine Self-administration

2020 ◽  
Vol 87 (11) ◽  
pp. 992-1000 ◽  
Author(s):  
Michel Engeln ◽  
Swarup Mitra ◽  
Ramesh Chandra ◽  
Utsav Gyawali ◽  
Megan E. Fox ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Specific Role ◽  
Medium Spiny Neurons ◽  
Self Administration ◽  
Spiny Neurons

scholarly journals Trafficking of calcium-permeable and calcium-impermeable AMPA receptors in nucleus accumbens medium spiny neurons co-cultured with prefrontal cortex neurons

2017 ◽  
Vol 116 ◽  
pp. 224-232 ◽  
Author(s):  
Craig T. Werner ◽  
Conor H. Murray ◽  
Jeremy M. Reimers ◽  
Niravkumar M. Chauhan ◽  
Kenneth K.Y. Woo ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Ampa Receptors ◽  
Medium Spiny Neurons ◽  
Spiny Neurons

scholarly journals Presence of Inhibitory Glycinergic Transmission in Medium Spiny Neurons in the Nucleus Accumbens

2018 ◽  
Vol 11 ◽  
Author(s):  
Braulio Muñoz ◽  
Gonzalo E. Yevenes ◽  
Benjamin Förstera ◽  
David M. Lovinger ◽  
Luis G. Aguayo
Keyword(s):  
Nucleus Accumbens ◽  
Medium Spiny Neurons ◽  
Spiny Neurons

Pitx3 Deficiency in Mice Affects Cholinergic Modulation of GABAergic Synapses in the Nucleus Accumbens

2006 ◽  
Vol 96 (4) ◽  
pp. 2034-2041 ◽  
Author(s):  
Mischa de Rover ◽  
Johannes C. Lodder ◽  
Marten P. Smidt ◽  
Arjen B. Brussaard
Keyword(s):  
Nucleus Accumbens ◽  
Medium Spiny Neurons ◽  
Wild Type ◽  
Cholinergic Modulation ◽  
Firing Patterns ◽  
Neural Adaptations ◽  
Cholinergic Interneurons ◽  
Spiny Neurons ◽  
Gating Mechanism ◽  
Deficient Mice

We investigated to what extent Pitx3 deficiency, causing hyperdopaminergic transmission in the nucleus accumbens microcircuitry, may lead to developmental changes. First, spontaneous firing activity of cholinergic interneurons in the nucleus accumbens was recorded in vitro. Firing patterns in the Pitx3-deficient mice were more variable and intrinsically different from those observed in wild-type mice. Next, to test whether the irregular firing patterns observed in mutant mice affected the endogenous nicotinic modulation of the GABAergic input of medium spiny neurons, we recorded spontaneous GABAergic inputs to these cells before and after the application of the nicotinic receptor blocker mecamylamine. Effects of mecamylamine were found in slices of either genotype, but in a rather inconsistent manner. Possibly this was attributable to heterogeneity in firing of nearby cholinergic interneurons. Thus paired recordings of cholinergic interneurons and medium spiny neurons were performed to more precisely control the experimental conditions of the cholinergic modulation of GABAergic synaptic transmission. We found that controlling action potential firing in cholinergic neurons leads to a conditional increase in GABAergic input frequency in wild-type mice but not in Pitx3-deficient mice. We conclude that Pitx3-deficient mice have neural adaptations at the level of the nucleus accumbens microcircuitry that in turn may have behavioral consequences. It is discussed to what extent dopamine release in the nucleus accumbens may be a long-term gating mechanism leading to alterations in cholinergic transmission in the nucleus accumbens, in line with previously reported neural adaptations found as consequences of repeated drug treatment in rodents.

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