scholarly journals Coordinated postnatal maturation of striatal cholinergic interneurons and dopamine release dynamics in mice

2020 ◽  
Author(s):  
Avery McGuirt ◽  
Ori Lieberman ◽  
Michael Post ◽  
Irena Pigulevskiy ◽  
David Sulzer
Keyword(s):  
Postnatal Development ◽  
Dopamine Release ◽  
Postnatal Period ◽  
Reward Processing ◽  
Developmental Trajectory ◽  
Synaptic Activity ◽  
Dopamine Neurons ◽  
Postnatal Maturation ◽  
Cholinergic Interneurons ◽  
Cholinergic Interneuron

AbstractDynamic changes in motor abilities and motivated behaviors occur during the juvenile and adolescent periods. The striatum is a subcortical nucleus critical for action selection, motor learning and reward processing. Its tonically active cholinergic interneuron (ChI) is an integral regulator of the synaptic activity of other striatal neurons, as well as afferent axonal projections of midbrain dopamine neurons. Thalamic and dopaminergic inputs initiate pauses in ChI firing following salient sensory cues that are extended for several hundred milliseconds by intrinsic regenerative currents. Here, we characterize the electrophysiological and morphological features of ChIs during mouse postnatal development. We demonstrate that ChI spontaneous activity increases with age while the duration of the pause in firing induced by depolarizing inputs decreases during postnatal development. Maturation of ChI activity is driven by two distinct physiological changes: decreased amplitude of the afterhypolarization between P14 and P18 and and increased Ih conductance between the late postnatal period and adulthood. Finally, we uncover postnatal changes in dopamine release properties that are mediated by cholinergic signalling. At P10, striatal dopamine release is diminished compared to the adult, but our data show efficient summation of dopamine relase evoked by multiple grouped stimuli that subsides by P28. Blockade of nictonic acetylcholine receptors enhances release summation in mice older than P28 but has little effect at P10. These data demonstrate a physiological maturation of ChI activity and indicate a reciprocal interaction between the postnatal maturation of striatal ChI and dopamine neurotransmission.Significance StatementMotor skills and motivated behavior regimes develop rapidly during the postnatal period. The functional development of the striatal cholinergic interneuron (ChI), which contributes to these behaviors in adulthood, remains unexplored. In this study, we tracked the ontogeny of spontaneous ChI activity and cellular morphology, as well as the developmental trajectory of ion conductances characteristic to this population. We further report a developmental link between ChI activity and dopamine release, revealing a change in the frequency-dependence of dopamine release during the early postnatal period that is mediated by cholinergic signaling. This study provides evidence that striatal microcircuits are dynamic during the postnatal period and that they undergo coordinated maturation.

scholarly journals Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing

Cell Reports ◽  
2012 ◽  
Vol 2 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Roger Cachope ◽  
Yolanda Mateo ◽  
Brian N. Mathur ◽  
James Irving ◽  
Hui-Ling Wang ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Reward Processing ◽  
Selective Activation ◽  
Cholinergic Interneurons

scholarly journals Cell-intrinsic effects of TorsinA(ΔE) disrupt dopamine release in a mouse model of DYT1-TOR1A dystonia

2020 ◽  
Author(s):  
Anthony M. Downs ◽  
Xueliang Fan ◽  
Radhika Kadakia ◽  
Yuping Donsante ◽  
H.A. Jinnah ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Ex Vivo ◽  
Dopamine Neurons ◽  
Striatal Dopamine ◽  
Cholinergic Interneurons ◽  
Base Pair Deletion ◽  
Presynaptic Mechanisms ◽  
Conditional Expression ◽  
Striatal Dopamine Release

ABSTRACTDYT1-TOR1A dystonia is an inherited dystonia caused by a three base-pair deletion in the TOR1A gene (TOR1AΔE). Although the mechanisms underlying the dystonic movements are largely unknown, abnormalities in striatal dopamine and acetylcholine neurotransmission are consistently implicated whereby dopamine release is reduced while cholinergic tone is increased. Because striatal cholinergic neurotransmission mediates dopamine release, it is not known if the dopamine release deficit is mediated indirectly by abnormal acetylcholine neurotransmission or if Tor1a(ΔE) acts directly within dopaminergic neurons to attenuate release. To dissect the microcircuit that governs the deficit in dopamine release, we conditionally expressed Tor1a(ΔE) in either dopamine neurons or cholinergic interneurons in mice and assessed striatal dopamine release using ex vivo fast scan cyclic voltammetry or dopamine efflux using in vivo microdialysis. Conditional expression of Tor1a(ΔE) in cholinergic neurons did not affect striatal dopamine release. In contrast, conditional expression of Tor1a(ΔE) in dopamine neurons reduced dopamine release to 50% of normal, which is comparable to the deficit in Tor1a+/ΔE knockin mice that express the mutation ubiquitously. Despite the deficit in dopamine release, we found that the Tor1a(ΔE) mutation does not cause obvious nerve terminal dysfunction as other presynaptic mechanisms, including electrical excitability, vesicle recycling/refilling, Ca2+ signaling, D2 dopamine autoreceptor function and GABAB receptor function, are intact. Although the mechanistic link between Tor1a(ΔE) and dopamine release is unclear, these results clearly demonstrate that the defect in dopamine release is caused by the action of the Tor1a(ΔE) mutation within dopamine neurons.

scholarly journals Coordinated postnatal maturation of striatal cholinergic interneurons and dopamine release dynamics in mice

2021 ◽  
pp. JN-RM-0755-20
Author(s):  
Avery McGuirt ◽  
Michael Post ◽  
Irena Pigulevskiy ◽  
David Sulzer ◽  
Ori Lieberman
Keyword(s):  
Dopamine Release ◽  
Postnatal Maturation ◽  
Cholinergic Interneurons

scholarly journals Distinct Expression Patterns Predict Differential Roles of the miRNA-Binding Proteins, Lin28 and Lin28b, in the Mouse Testis: Studies During Postnatal Development and in a Model of Hypogonadotropic Hypogonadism

Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1321-1336 ◽  
Author(s):  
Francisco Gaytan ◽  
Susana Sangiao-Alvarellos ◽  
María Manfredi-Lozano ◽  
David García-Galiano ◽  
Francisco Ruiz-Pino ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Binding Proteins ◽  
Rna Binding ◽  
Hypogonadotropic Hypogonadism ◽  
Expression Patterns ◽  
Mouse Testis ◽  
Null Mouse ◽  
Cellular Distribution ◽  
Protein Distribution ◽  
Postnatal Maturation

Abstract Lin28 (also termed Lin28a) and Lin28b are related RNA-binding proteins, involved in the control of microRNA synthesis, especially of the let-7 family, with putative functions in early (embryo) development. However, their roles during postnatal maturation remain ill defined. Despite the general assumption that Lin28 and Lin28b share similar targets and functions, conclusive demonstration of such redundancy is still missing. In addition, recent observations suggest a role of Lin28 proteins in mammalian reproduction, which is yet to be defined. We document herein the patterns of RNA expression and protein distribution of Lin28 and Lin28b in mouse testis during postnatal development and in a model of hypogonadotropic hypogonadism as a result of inactivation of the kisspeptin receptor, Gpr54. Lin28 and Lin28b mRNAs were expressed in mouse testis across postnatal maturation, but their levels disparately varied between neonatal and pubertal periods, with peak Lin28 levels in infantile testes and sustained elevation of Lin28b mRNA in young adult male gonads, where relative levels of let-7a and let-7b miRNAs were significantly suppressed. In addition, Lin28 peptides displayed totally different patterns of cellular distribution in mouse testis: Lin28 was located in undifferentiated and type-A1 spermatogonia, whereas Lin28b was confined to spermatids and interstitial Leydig cells. These profiles were perturbed in Gpr54 null mouse testis, which showed preserved but irregular Lin28 signal and absence of Lin28b peptide, which was rescued by administration of gonadotropins, mainly hCG (as super-agonist of LH). In addition, increased relative levels of Lin28, but not Lin28b, mRNA and of let-7a/let-7b miRNAs were observed in Gpr54 KO mouse testes. Altogether, our data are the first to document the divergent patterns of cellular distribution and mRNA expression of Lin28 and Lin28b in the mouse testis along postnatal maturation and their alteration in a model of congenital hypogonadotropic hypogonadism. Our findings suggest distinct functional roles of these two related, but not overlapping, miRNA-binding proteins in the male gonad.

scholarly journals The tectonigral pathway regulates appetitive locomotion in predatory hunting in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meizhu Huang ◽  
Dapeng Li ◽  
Xinyu Cheng ◽  
Qing Pei ◽  
Zhiyong Xie ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Dopamine Release ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuronal Circuitry ◽  
Locomotion Speed ◽  
Brain Circuit ◽  
Goal Directed Behavior

AbstractAppetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior—predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.

Sign in / Sign up

Export Citation Format

Share Document