Macey-Dare, A. | Search bioRxiv

bioRxiv2019

Distinct neural progenitor pools in the ventral telencephalon generate diversity in striatal spiny projection neurons

Heterogeneous populations of neural progenitors in the embryonic lateral ganglionic eminence (LGE) generate all GABAergic spiny projection neurons (SPNs) found in the striatum. Here we investigate how this diversity in neural progenitors relates to diversity of adult striatal neurons and circuits. Using a combination of in utero electroporation to fluorescently pulse-label striatal neural progenitors in the LGE, brain slice electrophysiology, electrical and optogenetic circuit mapping and immunohistochemistry, we characterise a population of neural progenitors enriched for apical intermediate progenitors (aIPs) and a distinct population of other progenitors (OPs) and their neural offspring. We find that neural progenitor origin has subtle but significant effects on the properties of striatal SPNs. Although aIP and OP progenitors can both generate D1-expressing direct pathway as well as D2-expressing indirect pathway SPNs found intermingled in the striatum, the aIP derived SPNs are found in more medial aspects of the striatum, exhibit more complex dendritic arbors with higher spine density and differentially sample cortical input. Moreover, optogenetic circuit mapping of the aIP derived neurons show that they further integrate within striatal circuits and innervate both local D1 and D2 SPNs. These results show that it is possible to fluorescently pulse-label distinct neural progenitor pools within the LGE and provide the first evidence that neural progenitor heterogeneity can contribute to the diversity of striatal SPNs.

neuroscience↗

bioRxiv2018

Early postnatal development of the cellular and circuit properties of striatal D1 and D2 spiny projection neurons

A dysfunctional striatum is thought to contribute to neurodevelopmental disorders such as ADHD, Tourettes syndrome and OCD. Insight into these disorders is reliant on an understanding of the normal development of the striatal cellular and circuit properties. Here we combined whole-cell patch-clamp electrophysiology and anatomical reconstructions of D1 and D2 striatal projection neurons (SPNs) in brain slices to characterize the development of the electrophysiological and morphological properties as well as their long-range and local inputs during the first three postnatal weeks. Overall, we find that many properties develop in parallel but we make several key observations. Firstly, that the electrophysiological properties of young D1 SPNs are more mature and that distinctions between D1 and D2 SPNs become apparent in the second postnatal week. Secondly, that dendrites and spines as well as excitatory inputs from cortex develop in parallel with cortical inputs exhibiting a prolonged period of maturation involving changes in postsynaptic glutamate receptors. Lastly, that initial local connections between striatal SPNs consist of gap junctions, which are gradually replaced by inhibitory synaptic connections. Interestingly, relative biases in inhibitory synaptic connectivity seen between SPNs in adulthood, such as a high connectivity between D2 SPNs, are already evident in the second postnatal week. Combined, these results provide an experimental framework for future investigations of striatal neurodevelopmental disorders and show that many of the cellular and circuit properties are established in the first and second postnatal weeks suggesting intrinsic programs guide their development.\n\nSignificance StatementNormal brain development involves the formation of neurons, which develop correct electrical and morphological properties and are precisely connected with each other in a neural circuit. In neurodevelopmental disorders these processes go awry leading to behavioral and cognitive problems later in life. Here we provide for the first time a detailed quantitative description of the cellular and circuit properties of the two main neuron types of the striatum during the first postnatal weeks. This can form an experimental framework for future studies into neurodevelopmental disorders. We find that most of the properties for both types of striatal neuron develop in parallel and are already established by the second postnatal week suggesting a key role for intrinsic programs in guiding their development.

neuroscience↗