A comprehensive excitatory input map of the striatum reveals novel functional organization

Hunnicutt, Barbara J.; Jongbloets, Bart C.; Birdsong, William T.; Gertz, Katrina J; Zhong, Haining; Mao, Tianyi

doi:10.7554/elife.19103

Cited by 427 publications

(553 citation statements)

References 68 publications

Supporting

Mentioning

503

Contrasting

Order By: Relevance

“…Although it has long been known that both the mPFC and BLA project to the DMS (Corbit et al, 2013; Hunnicutt et al, 2016; Kelley et al, 1982; McDonald, 1991; Oh et al, 2014; Pan et al, 2010; Wall et al, 2013), we demonstrated for the first time that both inputs overlapped in some DMS areas and targeted the same neuronal population. Previous studies used a single tracer to examine either the mPFC or BLA input; in this study, we employed two viruses encoding different fluorescence proteins (i.e., GFP and tdTomato) to label mPFC and BLA afferents in the same section.…”

Section: Discussionmentioning

confidence: 57%

“…To achieve this goal, we first examined whether the Chronos-mediated mPFC input was selectively activated by 405-nm light and the Chrimson-mediated BLA input by 590-nm light. Accumulating evidence suggests that the mPFC projects mainly to the anterior to middle region of the DMS and the BLA innervates the middle-posterior region (Corbit et al, 2013; Hunnicutt et al, 2016; Kelley et al, 1982; McDonald, 1991; Oh et al, 2014; Pan et al, 2010; Wall et al, 2013). We recorded neurons in an anterior DMS area that contained predominantly Chronos-GFP-containing fibers (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Alcohol induces input-specific aberrant synaptic plasticity in the rat dorsomedial striatum

Barbee

Wang

et al. 2017

Neuropharmacology

View full text Add to dashboard Cite

Accumulated evidence suggests that the dorsomedial striatum (DMS) of the basal ganglia plays an essential role in pathological excessive alcohol consumption. The DMS receives multiple glutamatergic inputs. However, whether and how alcohol consumption distinctly affects these excitatory afferents to the DMS remains unknown. Here, we used optogenetics to selectively activate the rat medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) inputs in DMS slices, and measured the effects of alcohol consumption on glutamatergic transmission in these corticostriatal and amygdalostriatal circuits. We found that excessive alcohol consumption increased AMPA receptor- and NMDA receptor (NMDAR)-mediated neurotransmission, as well as the GluN2B/NMDAR ratio, at the corticostriatal input to the DMS. The probability of glutamate release was increased selectively at the amygdalostriatal input. Interestingly, we discovered that paired activation of the mPFC and BLA inputs using dual-channel optogenetics induced robust long-term potentiation (LTP) of the corticostriatal input to the DMS. Taken together, these results indicate that excessive alcohol consumption potentiates glutamatergic transmission via a postsynaptic mechanism for the corticostriatal input and via a presynaptic mechanism for the amygdalostriatal input. These changes may in turn contribute to pathological alcohol consumption.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Alcohol induces input-specific aberrant synaptic plasticity in the rat dorsomedial striatum

Barbee

Wang

et al. 2017

Neuropharmacology

View full text Add to dashboard Cite

show abstract

“…Electrophysiological studies have used oblique horizontal slices to activate each pathway separately. However, reports employing this technique have yielded contradictory results, possibly due to species and procedural differences (Smeal et al, 2006; Ding et al, 2008; Smeal et al, 2008) or to the lack of sub-regional specificity (Hunnicutt et al, 2016). With the advent of optogenetics these challenges have been largely overcome (Ellender et al, 2011; Sciamanna et al, 2015; Kolodziejczyk and Raymond, 2016).…”

Section: Introductionmentioning

confidence: 99%

Differential electrophysiological and morphological alterations of thalamostriatal and corticostriatal projections in the R6/2 mouse model of Huntington's disease

Parievsky

Moore

Kamdjou

et al. 2017

Neurobiology of Disease

View full text Add to dashboard Cite

Huntington’s disease (HD) is a fatal genetic disorder characterized by cell death of medium-sized spiny neurons (MSNs) in the striatum, traditionally attributed to excessive glutamate inputs and/or receptor sensitivity. While changes in corticostriatal projections have typically been studied in mouse models of HD, morphological and functional alterations in thalamostriatal projections have received less attention. In this study, an adeno-associated virus expressing channelrhodopsin-2 under the calcium/calmodulin-dependent protein kinase IIα promoter was injected into the sensorimotor cortex or the thalamic centromedian-parafascicular nuclear complex in the R6/2 mouse model of HD, to permit selective activation of corticostriatal or thalamostriatal projections, respectively. In symptomatic R6/2 mice, peak amplitudes and areas of corticostriatal glutamate AMPA and NMDA receptor-mediated responses were reduced. In contrast, although peak amplitudes of AMPA and NMDA receptor-mediated thalamostriatal responses also were reduced, the areas remained unchanged due to an increase in response decay times. Blockade of glutamate reuptake further increased response areas and slowed rise and decay times of NMDA responses. These effects appeared more pronounced at thalamostriatal synapses of R6/2 mice, suggesting increased activation of extrasynaptic NMDA receptors. In addition, the probability of glutamate release was higher at thalamostriatal than corticostriatal synapses, particularly in R6/2 mice. Morphological studies indicated that the density of all excitatory synaptic contacts onto MSNs was reduced, which matches the basic electrophysiological findings of reduced amplitudes. There was a consistent reduction in the area of spines but little change in presynaptic terminal size, indicating that the postsynaptic spine may be more significantly affected than presynaptic terminals. These results highlight the significant and differential contribution of the thalamostriatal projection to glutamate excitotoxicity in HD.

show abstract

“…This functional hypothesis is also supported by the fact that the striatum receives topographically organized cortical projections (Hunnicutt et al . ) and shows territory‐specific molecular reactivity (Gangarossa et al . ).…”

Section: Discussionmentioning

confidence: 99%

VGLUT3 gates psychomotor effects induced by amphetamine

Mansouri-Guilani

Bernard

Vigneault

et al. 2019

Journal of Neurochemistry

View full text Add to dashboard Cite

Several subtypes of modulatory neurons co‐express vesicular glutamate transporters (VGLUTs) in addition to their cognate vesicular transporters. These neurons are believed to establish new forms of neuronal communication. The atypical VGLUT3 is of particular interest since in the striatum this subtype is found in tonically active cholinergic interneurons (TANs) and in a subset of 5‐HT fibers. The striatum plays a major role in psychomotor effects induced by amphetamine. Whether and how VGLUT3‐operated glutamate/ACh or glutamate/5HT co‐transmissions modulates psychostimulants‐induced maladaptive behaviors is still unknown. Here, we investigate the involvement of VGLUT3 and glutamate co‐transmission in amphetamine‐induced psychomotor effects and stereotypies. Taking advantage of constitutive and cell‐type specific VGLUT3‐deficient mouse lines, we tackled the hypothesis that VGLUT3 could gate psychomotor effects (locomotor activity and stereotypies) induced by acute or chronic administration of amphetamine. Interestingly, VGLUT3‐null mice demonstrated blunted amphetamine‐induced stereotypies as well as reduced striatal ∆FosB expression. VGLUT3‐positive varicosities within the striatum arise in part from 5HT neurons. We tested the involvement of VGLUT3 deletion in serotoninergic neurons in amphetamine‐induced stereotypies. Mice lacking VGLUT3 specifically in 5HT fibers showed no alteration to amphetamine sensitivity. In contrast, specific deletion of VGLUT3 in cholinergic neurons partially phenocopied the effects observed in the constitutive knock‐out mice. Our results show that constitutive deletion of VGLUT3 modulates acute and chronic locomotor effects induced by amphetamine. They point to the fact that the expression of VGLUT3 in multiple brain areas is pivotal in gating amphetamine‐induced psychomotor adaptations. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

show abstract

A comprehensive excitatory input map of the striatum reveals novel functional organization

Cited by 427 publications

References 68 publications

Alcohol induces input-specific aberrant synaptic plasticity in the rat dorsomedial striatum

Alcohol induces input-specific aberrant synaptic plasticity in the rat dorsomedial striatum

Differential electrophysiological and morphological alterations of thalamostriatal and corticostriatal projections in the R6/2 mouse model of Huntington's disease

VGLUT3 gates psychomotor effects induced by amphetamine

Contact Info

Product

Resources

About