Onset of pup locomotion coincides with loss of NR2C/D-mediated cortico-striatal EPSCs and dampening of striatal network immature activity

Abstract

Adult motor coordination requires strong coincident cortical excitatory input to hyperpolarized medium spiny neurons (MSNs), the dominant neuronal population of the striatum. However, cortical and subcortical neurons generate during development large ongoing patterns required for activity-dependent construction of networks. This raises the question of whether immature MSNs have adult features from early stages or whether they generate immature patterns that are timely silenced to enable locomotion. Using a wide range of techniques including dynamic two-photon imaging, whole cell or single-channel patch clamp recording in slices from Nkx2.1-GFP mice, we now report a silencing of MSNs that timely coincides with locomotion. At embryonic stage (as early as E16) and during early postnatal days, genetically identified MSNs have a depolarized resting membrane potential, a high input resistance and lack both inward rectifying (IKIR) and early slowly inactivating (ID) potassium currents. They generate intrinsic voltage-gated clustered calcium activity without synaptic components. From postnatal days 5–7, the striatal network transiently generates synapse-driven giant depolarizing potentials when activation of cortical inputs evokes long lasting EPSCs in MSNs. Both are mediated by NR2C/D-receptors. These immature features are abruptly replaced by adult ones before P10: MSNs express IKIR and ID and generate short lasting, time-locked cortico-striatal AMPA/NMDA EPSCs with no NR2C/D component. This shift parallels the onset of quadruped motion by the pup. Therefore, MSNs generate immature patterns that are timely shut off to enable the coordination of motor programs.

Contribution of different classes of glutamate receptors in the corticostriatal polysynaptic responses from striatal direct and indirect projection neurons

“…The postsynaptic presence of an ACET-sensitive component with a physiological stimulus (release of endogenous glutamate) confirms previous suggestions about their potential postsynaptic importance [2,51]. …”

“…Post-synaptic KA-receptors are present in striatal neurons [2,39,43]. Here, we asked whether some class of KA-receptors could be synaptically activated by cortical afferents during suprathreshold corticostriatal responses (i.e.…”

“…: with endogenous glutamate release). The physiological response of native KA-receptors may have different kinetics than AMPA-receptors [2,44,45] and we wanted to observe if this is true for corticostriatal responses. ACET (see Methods) has been reported as a highly selective antagonist for GluK1 KA receptor subunits in expression systems [46-48] and there are GluK1 subunits in the striatum [5,49] as reported by PCR techniques.…”

Haploinsufficiency of Dmxl2, Encoding a Synaptic Protein, Causes Infertility Associated with a Loss of GnRH Neurons in Mouse

“…We analyzed the gait and exploratory behavior of these mice in an open-field system [30]. No significant difference of the gait between Dmxl2 tm1a/wt mice and their WT littermates was observed.…”

Sildenafil Mediates Blood-Flow Redistribution and Neuroprotection After Neonatal Hypoxia-Ischemia

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