scholarly journals Multiscale imaging characterization of dopamine transporter knockout mice reveals regional alterations in spine density of medium spiny neurons

2011 ◽  
Vol 1390 ◽  
pp. 41-49 ◽  
Author(s):  
M.L. Berlanga ◽  
D.L. Price ◽  
B.S. Phung ◽  
R. Giuly ◽  
M. Terada ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Knockout Mice ◽  
Medium Spiny Neurons ◽  
Spine Density ◽  
Spiny Neurons ◽  
Multiscale Imaging ◽  
Imaging Characterization

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.

Changes in Dendritic Spine Density and Inhibitory Perisomatic Connectivity onto Medium Spiny Neurons in l-Dopa-Induced Dyskinesia

2019 ◽  
Vol 56 (9) ◽  
pp. 6261-6275 ◽  
Author(s):  
G. Gomez ◽  
M. V. Escande ◽  
L. M. Suarez ◽  
L. Rela ◽  
J. E. Belforte ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Medium Spiny Neurons ◽  
Spine Density ◽  
Spiny Neurons ◽  
Dendritic Spine Density

scholarly journals Mushroom spine dynamics in medium spiny neurons of dorsal striatum associated with memory of moderate and intense training

2016 ◽  
Vol 113 (42) ◽  
pp. E6516-E6525 ◽  
Author(s):  
Paola C. Bello-Medina ◽  
Gonzalo Flores ◽  
Gina L. Quirarte ◽  
James L. McGaugh ◽  
Roberto A. Prado Alcalá
Keyword(s):  
Memory Consolidation ◽  
Dorsal Striatum ◽  
Inhibitory Avoidance ◽  
Brain Structures ◽  
Brain Regions ◽  
Medium Spiny Neurons ◽  
Spine Density ◽  
Spiny Neurons ◽  
Intense Training ◽  
Transfer Of Information

A growing body of evidence indicates that treatments that typically impair memory consolidation become ineffective when animals are given intense training. This effect has been obtained by treatments interfering with the neural activity of several brain structures, including the dorsal striatum. The mechanisms that mediate this phenomenon are unknown. One possibility is that intense training promotes the transfer of information derived from the enhanced training to a wider neuronal network. We now report that inhibitory avoidance (IA) induces mushroom spinogenesis in the medium spiny neurons (MSNs) of the dorsal striatum in rats, which is dependent upon the intensity of the foot-shock used for training; that is, the effect is seen only when high-intensity foot-shock is used in training. We also found that the relative density of thin spines was reduced. These changes were evident at 6 h after training and persisted for at least 24 h afterward. Importantly, foot-shock alone did not increase spinogenesis. Spine density in MSNs in the accumbens was also increased, but the increase did not correlate with the associative process involved in IA; rather, it resulted from the administration of the aversive stimulation alone. These findings suggest that mushroom spines of MSNs of the dorsal striatum receive afferent information that is involved in the integrative activity necessary for memory consolidation, and that intense training facilitates transfer of information from the dorsal striatum to other brain regions through augmented spinogenesis.

Characterization of acid-sensing ion channels in medium spiny neurons of mouse striatum

Neuroscience ◽  
2009 ◽  
Vol 162 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Q. Jiang ◽  
M.-H. Li ◽  
C.J. Papasian ◽  
D. Branigan ◽  
Z.-G. Xiong ◽  
...  
Keyword(s):  
Ion Channels ◽  
Medium Spiny Neurons ◽  
Spiny Neurons ◽  
Mouse Striatum ◽  
Acid Sensing Ion Channels

scholarly journals MPTP Neurotoxicity and Testosterone Induce Dendritic Remodeling of Striatal Medium Spiny Neurons in the C57Bl/6 Mouse

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Eleni Antzoulatos ◽  
Michael W. Jakowec ◽  
Giselle M. Petzinger ◽  
Ruth I. Wood
Keyword(s):  
Tyrosine Hydroxylase ◽  
Left Hemisphere ◽  
Dendritic Morphology ◽  
Neuronal Morphology ◽  
Medium Spiny Neurons ◽  
Protective Effects ◽  
Spine Density ◽  
Spiny Neurons ◽  
The Right ◽  
Gonadal Status

Nigrostriatal damage is increased in males relative to females. While estrogen is neuroprotective in females, less is known about potential protective effects of testosterone in males. We determined if castration enhances neuronal injury to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Castrates or sham-castrated mice were sacrificed 1 week following injection of MPTP (4×20 mg/kg) or saline (n=11-12/group). The right striatum was immunostained for tyrosine hydroxylase (TH). The left hemisphere was stained by Golgi Cox to quantify neuronal morphology in medium spiny neurons (MSNs) of the dorsolateral striatum. MPTP reduced TH, but there was no effect of castration and no interaction. For MSN dendritic morphology, MPTP decreased the highest branch order and increased spine density on 2nd-order dendrites. Castrated males had shorter 5th-order dendrites. However, there was no interaction between gonadal status and MPTP. Thus, castration and MPTP exert nonoverlapping effects on MSN morphology with castration acting on distal dendrites and MPTP acting proximally.

scholarly journals A novel role for the actin-binding protein drebrin in regulating opiate addiction

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jennifer A. Martin ◽  
Craig T. Werner ◽  
Swarup Mitra ◽  
Ping Zhong ◽  
Zi-Jun Wang ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Binding Protein ◽  
Actin Binding ◽  
Medium Spiny Neurons ◽  
Spine Density ◽  
Self Administration ◽  
Actin Binding Protein ◽  
Cellular Events ◽  
Behavioral Adaptations ◽  
Spiny Neurons

Abstract Persistent transcriptional and morphological events in the nucleus accumbens (NAc) and other brain reward regions contribute to the long-lasting behavioral adaptations that characterize drug addiction. Opiate exposure reduces the density of dendritic spines on medium spiny neurons of the NAc; however, the underlying transcriptional and cellular events mediating this remain unknown. We show that heroin self-administration negatively regulates the actin-binding protein drebrin in the NAc. Using virus-mediated gene transfer, we show that drebrin overexpression in the NAc is sufficient to decrease drug seeking and increase dendritic spine density, whereas drebrin knockdown potentiates these effects. We demonstrate that drebrin is transcriptionally repressed by the histone modifier HDAC2, which is relieved by pharmacological inhibition of histone deacetylases. Importantly, we demonstrate that heroin-induced adaptations occur only in the D1+ subset of medium spiny neurons. These findings establish an essential role for drebrin, and upstream transcriptional regulator HDAC2, in opiate-induced plasticity in the NAc.

scholarly journals Morphology of Human Nucleus Accumbens Neurons Based on the Immunohistochemical Expression of Gad67

2016 ◽  
Vol 17 (4) ◽  
pp. 297-302
Author(s):  
Maja Sazdanovic ◽  
Slobodanka Mitrovic ◽  
Milos Todorovic ◽  
Maja Vulovic ◽  
Dejan Jeremic ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Pyramidal Neurons ◽  
Immunohistochemical Analysis ◽  
Medium Spiny Neurons ◽  
Immunohistochemical Expression ◽  
Spiny Neurons ◽  
Different Types ◽  
Human Brains

Abstract The nucleus accumbens is a part of the ventral striatum along with the caudate nucleus and putamen. The role of the human nucleus accumbens in drug addiction and other psychiatric disorders is of great importance. The aim of this study was to characterize medium spiny neurons in the nucleus accumbens according to the immunohistochemical expression of GAD67. This study was conducted on twenty human brains of both sexes between the ages of 20 and 75. The expression of GAD67 was assessed immunohistochemically, and the characterization of the neurons was based on the shape and size of the soma and the number of impregnated primary dendrites. We showed that neurons of the human nucleus accumbens expressed GAD67 in the neuron soma and in the primary dendrites. An analysis of the cell body morphology revealed the following four different types of neurons: fusiform neurons, fusiform neurons with lateral dendrites, pyramidal neurons and multipolar neurons. An immunohistochemical analysis showed a strong GAD67 expression in GABAergic medium spiny neurons, which could be classifi ed into four different types, and these neurons morphologically correlated with those described by the Golgi study.

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