scholarly journals Neuron-type specificity of dorsal raphe projections to ventral tegmental area

2021 ◽  
Author(s):  
Anna J. Chang ◽  
Lihua Wang ◽  
Federica Lucantonio ◽  
Maya Adams ◽  
Andy Lemire ◽  
...  
Keyword(s):  
Single Cell ◽  
Ventral Tegmental Area ◽  
Cell Types ◽  
Dorsal Raphe ◽  
Physiological Data ◽  
Differential Distribution ◽  
Ventral Tegmental ◽  
And Behavior ◽  
Long Timescales ◽  
Dorsal Raphé

The midbrain dorsal raphe (DR) and ventral tegmental area (VTA) contain two of the brain’s main ascending neuromodulatory transmitters: serotonin and dopamine. We studied the pathway from DR to VTA using single-cell RNA sequencing, anatomical tracing, and electrophysiology and behavior in mice. Single-cell sequencing confirmed a differential distribution of dopamine cell types between medial and lateral aspects of the VTA. This molecular diversity included differential expression of a subset of glutamatergic and serotonergic receptors. Anatomical data showed that distinct serotonergic and glutamatergic populations of DR neurons project to distinct medial-lateral locations in VTA. Physiological data showed that serotonergic neurons are positioned to excite putative dopaminergic neurons in lateral VTA on short timescales (within trial), and inhibit them on long timescales (on the next trial). Our results reveal precise anatomical specificity of DR projections to VTA, and suggest a functional role for serotonergic modulation of dopaminergic function across multiple timescales.

scholarly journals Rostral and Caudal Ventral Tegmental Area GABAergic Inputs to Different Dorsal Raphe Neurons Participate in Opioid Dependence

Neuron ◽  
2019 ◽  
Vol 101 (4) ◽  
pp. 748-761.e5 ◽  
Author(s):  
Yue Li ◽  
Chun-Yue Li ◽  
Wang Xi ◽  
Sen Jin ◽  
Zuo-Hang Wu ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Opioid Dependence ◽  
Dorsal Raphe ◽  
Ventral Tegmental ◽  
Dorsal Raphé ◽  
Raphe Neurons

scholarly journals Chronic methylphenidate treatment during adolescence has long-term effects on monoaminergic function

2018 ◽  
Vol 33 (1) ◽  
pp. 109-121 ◽  
Author(s):  
Mathieu Di Miceli ◽  
Adesina Omoloye ◽  
Benjamin Gronier
Keyword(s):  
Ventral Tegmental Area ◽  
Dorsal Raphe Nucleus ◽  
Late Adolescence ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Late Adolescent ◽  
Serotonin Neurons ◽  
Ventral Tegmental ◽  
Dorsal Raphé

Background: Psychostimulants like methylphenidate or D-amphetamine are often prescribed for attention deficit and hyperactivity disorders in children. Whether such drugs can be administered into a developing brain without consequences in adulthood is still an open question. Methods: Here, using in vivo extracellular electrophysiology in anesthetised preparations, combined with behavioural assays, we have examined the long-term consequences in adulthood of a chronic methylphenidate oral administration (5 mg/kg/day, 15 days) in early adolescent (post-natal day 28) and late adolescent (post-natal day 42) rats, by evaluating body weight change, sucrose preference (indicator of anhedonia), locomotor sensitivity to D-amphetamine and electrical activities of ventral tegmental area dopamine and dorsal raphe nucleus serotonin neurons. Results: Chronic methylphenidate treatment during early or late adolescence did not induce weight deficiencies and anhedonia-like behaviours at adulthood. However, it increased bursting activities of dorsal raphe nucleus serotonin neurons. Furthermore, chronic methylphenidate treatment during early but not during late adolescence enhanced D-amphetamine-induced rearing activity, as well as ventral tegmental area dopamine cell excitability (firing, burst and population activity), associated with a partial desensitisation of dopamine D2 auto-receptors. Conclusions: We have demonstrated here that early, but not late, adolescent exposure to oral methylphenidate may induce long-lasting effects on monoamine neurotransmission. The possible clinical implication of these data will be discussed.

scholarly journals A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons

2020 ◽  
Author(s):  
Benjamin W. Okaty ◽  
Nikita Sturrock ◽  
Yasmin Escobedo Lozoya ◽  
YoonJeung Chang ◽  
Rebecca A. Senft ◽  
...  
Keyword(s):  
Single Cell ◽  
Functional Organization ◽  
Dorsal Raphe ◽  
Molecular Heterogeneity ◽  
Electrophysiological Properties ◽  
Efferent Projections ◽  
Brainstem Raphe ◽  
And Behavior ◽  
Distinct Subtype ◽  
Dorsal Raphé

AbstractAmong the brainstem raphe nuclei, the dorsal raphe nucleus (DR) contains the greatest number of Pet1-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior and are often therapeutically targeted to treat affective disorders. Characterizing Pet1 neuron molecular heterogeneity and relating it to anatomy is vital for understanding DR functional organization, with potential to inform therapeutic separability. Here we use high-throughput and DR subdomain-targeted single-cell transcriptomics and intersectional genetic tools to map molecular and anatomical diversity of DR-Pet1 neurons. We describe up to fourteen neuron subtypes, many showing biased cell body distributions across the DR. We further show that P2ry1-Pet1 DR neurons – the most molecularly distinct subtype – possess unique efferent projections and electrophysiological properties. These data complement and extend previous DR characterizations, combining intersectional genetics with multiple transcriptomic modalities to achieve fine-scale molecular and anatomic identification of Pet1 neuron subtypes.

scholarly journals Glutamate NMDA receptors containing GluN2C subunit relay the reward signal of the ventral tegmental area upon dorsal raphe stimulation

2020 ◽  
Author(s):  
Giovanni Hernandez ◽  
Emmanuelle Poirier ◽  
Karim Lebied ◽  
Willemieke M Kouwenhoven ◽  
Daniel Lévesque ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Ventral Tegmental Area ◽  
Glutamate Transporter ◽  
Dorsal Raphe ◽  
Down Regulation ◽  
Brain Areas ◽  
Ventral Tegmental ◽  
Dorsal Raphé

AbstractBackgroundGlutamate relays the reward signal from the dorsal raphe (DR) to ventral tegmental area (VTA) dopamine (DA) neurons. However, its role is complex and not clearly understood. We measured NMDA receptors subunits expression in limbic brain areas and studied the effects of VTA down-regulation of GluN2C subunit-containing NMDA receptor on the reward signal that arises from DR electrical stimulation.MethodsVia qPCR, we identified the relative composition of the different GluN2 NMDA receptors subunits in several brain areas. Then we used fluorescent in situ hybridization (FISH) to evaluate the colocalization of Grin2c and Tyrosine hydroxylase (Th) mRNA in VTA neurons. To assess the role of GluN2C in reward pursuit; we downregulated this receptor using small interfering RNA (siRNA) in rats self-stimulating for electrical pulses delivered to the DR. To delineate further the specific role of GluN2C in relaying the reward signal, we pharmacologically altered the function of VTA NMDA receptors by either bilaterally microinjecting the NMDA receptor antagonist PPPA or the glutamate transporter inhibitor (GLT-1), Dhk.ResultsWe identified that GluN2C is the most abundant NMDA receptor subunit expressed in the VTA. FISH revealed that a substantial number of TH+ neurons colocalize with Grin2C. The siRNA manipulation produced a selective down-regulation of GluN2C and a significant reduction in reward pursuit. Interestingly, PPPA and DHK respectively enhanced and suppressed reward pursuit, but only in rats that received the non-active RNA sequence.ConclusionThe present results suggest that VTA Glutamate neurotransmission relays the reward signal initiated by DR stimulation by acting on GluN2C NMDA receptors.

scholarly journals Rostral and Caudal Ventral Tegmental Area GABAergic Inputs to Different Dorsal Raphe Neurons Participate in Opioid Dependence

Neuron ◽  
2021 ◽  
Vol 109 (23) ◽  
pp. 3893-3894
Author(s):  
Yue Li ◽  
Chun-Yue Li ◽  
Wang Xi ◽  
Sen Jin ◽  
Zuo-Hang Wu ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Opioid Dependence ◽  
Dorsal Raphe ◽  
Ventral Tegmental ◽  
Dorsal Raphé ◽  
Raphe Neurons
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