Glutamatergic synaptic currents of nigral dopaminergic neurons follow a postnatal developmental sequence

Constance Hammond,Robin Cloarec,Edouard Pearlstein,FranÃ§ois J. Michel,Laurie-Anne Gouty-Colomer

doi:10.3389/fncel.2015.00210

Abstract

The spontaneous activity pattern of adult dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc) results from interactions between intrinsic membrane conductances and afferent inputs. In adult SNc DA neurons, low-frequency tonic background activity is generated by intrinsic pacemaker mechanisms, whereas burst generation depends on intact synaptic inputs in particular the glutamatergic ones. Tonic DA release in the striatum during pacemaking is required to maintain motor activity, and burst firing evokes phasic DA release, necessary for cue-dependent learning tasks. However, it is still unknown how the firing properties of SNc DA neurons mature during postnatal development before reaching the adult state. We studied the postnatal developmental profile of spontaneous and evoked AMPA and NMDA (N-Methyl-D-aspartic acid) receptor-mediated excitatory postsynaptic currents (EPSCs) in SNc DA neurons in brain slices from immature (postnatal days P4–P10) and young adult (P30–P50) tyrosine hydroxylase (TH)-green fluorescent protein mice. We found that somato-dendritic fields of SNc DA neurons are already mature at P4–P10. In contrast, spontaneous glutamatergic EPSCs show a developmental sequence. Spontaneous NMDA EPSCs in particular are larger and more frequent in immature SNc DA neurons than in young adult ones and have a bursty pattern. They are mediated by GluN2B and GluN2D subunit-containing NMDA receptors. The latter generate long-lasting, DQP 1105-sensitive, spontaneous EPSCs, which are transiently recorded during this early period. Due to high NMDA activity, immature SNc DA neurons generate large and long lasting NMDA receptor-dependent (APV-sensitive) bursts in response to the stimulation of the subthalamic nucleus. We conclude that the transient high NMDA activity allows calcium influx into the dendrites of developing SNc DA neurons.

Highlights

The dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc, A9) are involved in the control of reward-related behavior and motor performances (Schultz, 2013)
AMPA Receptor-Mediated spontaneous EPSCs (sEPSCs) Follow a Postnatal Developmental Sequence We recorded sEPSCs (VH = –60 mV) at P4–P10 and at P30+ that were insensitive to APV (40 μM), the specific antagonist of NMDA receptors, but fully blocked by the addition of NBQX 1 μM, a preferential antagonist of AMPA receptors (n = 6, data not shown)
The AMPA/NMDA Ratio of Glutamatergic Receptor-Mediated excitatory postsynaptic currents (EPSCs) Follows a Developmental Sequence We investigated whether a change in NMDA current during development would be evidenced by a change in AMPA/NMDA ratio

Summary

Introduction

The dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc, A9) are involved in the control of reward-related behavior and motor performances (Schultz, 2013). The spontaneous activity pattern of adult SNc DA neurons results from the interactions between intrinsic and synaptic currents. In adult rodents in vivo, this varies between a slow, intrinsically generated, iGluR EPSCs in developing dopaminergic neurons pacemaker-like firing pattern and an irregular pattern with bursts triggered by the transient interaction between ionotropic glutamate receptors and voltage gated ionic channels (Bunney et al, 1973; Grace and Bunney, 1984a,b; Grace and Onn, 1989; Hyland et al, 2002; Fa et al, 2003; Deister et al, 2009). The firing rate and firing pattern of SNc neurons are major determinants of the levels of dopamine released from terminals. Burst firing greatly and transiently increases dopamine release (Gonon, 1988; Manley et al, 1992; Chergui et al, 1994; Grillner and Mercuri, 2002), which in turn promotes the corticostriatal plasticity necessary for habit-learning (Reynolds and Wickens, 2000; Centonze et al, 2001; Calabresi et al, 2007; Kreitzer and Malenka, 2008; Schultz, 2013)

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