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Differential contribution of Ih to the integration of excitatory synaptic inputs in substantia nigra pars compacta and ventral tegmental area dopaminergic neurons
Author(s) -
Masi Alessio,
Narducci Roberto,
Resta Francesco,
Carbone Carmen,
Kobayashi Kazuto,
Mannaioni Guido
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13066
Subject(s) - pars compacta , ventral tegmental area , substantia nigra , neuroscience , excitatory postsynaptic potential , dopaminergic , dopamine , neurotransmission , electrophysiology , chemistry , biology , inhibitory postsynaptic potential , biochemistry , receptor
The selective vulnerability of substantia nigra pars compacta ( SN c) dopaminergic ( DA ) neurons is an enigmatic trait of Parkinson's disease ( PD ), especially if compared to the remarkable resistance of closely related DA neurons in the neighboring ventral tegmental area ( VTA ). Overall evidence indicates that specific electrophysiological, metabolic and molecular factors underlie SN c vulnerability, although many pieces of the puzzle are still missing. In this respect, we recently demonstrated that 1‐methyl‐4‐phenylpyridinium ( MPP +), the active metabolite of the parkinsonizing toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine ( MPTP ), alters the electrophysiological properties of SN c DA neurons in vitro by inhibiting the hyperpolarization‐activated current (Ih). Here, we present an electrophysiological investigation of the functional role of Ih in the integration of synaptic inputs in identified SN c and VTA DA neurons, comparatively, in acute midbrain slices from TH ‐ GFP mice. We show that pharmacological suppression of Ih increases the amplitude and decay time of excitatory postsynaptic potentials, leading to temporal summation of multiple excitatory potentials at somatic level. Importantly, these effects are quantitatively more evident in SN c DA neurons. We conclude that Ih regulates the responsiveness to excitatory synaptic transmission in SN c and VTA DA neurons differentially. Finally, we present the hypothesis that Ih loss of function may be linked to PD trigger mechanisms, such as mitochondrial failure and ATP depletion, and act in concert with SN c‐specific synaptic connectivity to promote selective vulnerability.