Neurons gating behavior—developmental, molecular and functional features of neurons in the Substantia Nigra pars reticulata

Abstract

The Substantia Nigra pars reticulata (SNpr) is the major information output site of the basal ganglia network and instrumental for the activation and adjustment of movement, regulation of the behavioral state and response to reward. Due to both overlapping and unique input and output connections, the SNpr might also have signal integration capacity and contribute to action selection. How the SNpr regulates these multiple functions remains incompletely understood. The SNpr is located in the ventral midbrain and is composed primarily of inhibitory GABAergic projection neurons that are heterogeneous in their properties. In addition, the SNpr contains smaller populations of other neurons, including glutamatergic neurons. Here, we discuss regionalization of the SNpr, in particular the division of the SNpr neurons to anterior (aSNpr) and posterior (pSNpr) subtypes, which display differences in many of their features. We hypothesize that unique developmental and molecular characteristics of the SNpr neuron subtypes correlate with both region-specific connections and notable functional specializations of the SNpr. Variation in both the genetic control of the SNpr neuron development as well as signals regulating cell migration and axon guidance may contribute to the functional diversity of the SNpr neurons. Therefore, insights into the various aspects of differentiation of the SNpr neurons can increase our understanding of fundamental brain functions and their defects in neurological and psychiatric disorders, including movement and mood disorders, as well as epilepsy.

Striatonigral distribution of a fluorescent reporter following intracerebral delivery of genome editors

“…Expression of tdTomato in the SNpr was typically present in discrete clusters of fibers and limited to animals with total areas of striatal editing above approximately 1 mm 2 . The nonuniform distribution of tdTomato in the SNpr is consistent with previous descriptions of striatal inputs to the SNpr maintaining features of the striatal topographical organization ( Partanen and Achim, 2022 ). Tracing studies in rodents have shown that axons from GABAergic medium spiny neurons in the striatum are directed to defined longitudinal columns across the SNpr ( Deniau et al, 1996 ; Foster et al, 2021 ).…”

“…Editing of neuronal DNA in the striatum was required for visualization of tdTomato in the SNpr, as no animals in the NC-Scrambled group exhibited tdTomato expression in the SN. Approximately 95% of neurons in the striatum are medium spiny neurons ( Arlotta et al, 2005 ), which send inhibitory projections to the surrounding nuclei of the basal ganglia, including the SNpr ( Stephenson-Jones et al, 2012 ; Partanen and Achim, 2022 ). Our findings suggest that the tdTomato protein produced in the soma of genome edited striatal medium spiny neurons undergoes axonal anterograde transport to fill the cell cytoplasm and appear visible in fibers in the SNpr.…”

Striatonigral distribution of a fluorescent reporter following intracerebral delivery of genome editors

“…Approximately 95% of neurons in the striatum are medium spiny neurons (Arlotta et al, 2005), which send inhibitory projections to the surrounding nuclei of the basal Expression of tdTomato in the SNpr was typically present in discrete clusters of fibers and limited to animals with total areas of striatal editing above approximately 1 mm 2 . The nonuniform distribution of tdTomato in the SNpr is consistent with previous descriptions of striatal inputs to the SNpr maintaining features of the striatal topographical organization (Partanen and Achim, 2022). Tracing studies in rodents have shown that axons from GABAergic medium spiny neurons in the striatum are directed to defined longitudinal columns across the SNpr (Deniau et al, 1996;Foster et al, 2021).…”

Silencing of dentate gyrus inhibits mossy fiber sprouting and prevents epileptogenesis through NDR2 kinase in pentylenetetrazole kindling rat model of TLE

“…Substantia nigra is a mesencephalic structure inserted along several circuits which appear to play a key role in epilepsy [ 43 ]. The function of substantia nigra pars reticulata (SNpr) has been associated with the control of seizures.…”

“…Those findings indicated that NDR2 can be a bidirectional molecule regulating neurite outgrowth under different physiological and pathological conditions. Substantia nigra is a mesencephalic structure inserted along several circuits which appear to play a key role in epilepsy [43]. The function of substantia nigra pars reticulata (SNpr) has been associated with the control of seizures.…”