I(h) channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain

TY - JOUR

T1 - I(h) channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain

AU - Neuhoff, Henrike

AU - Neu, Axel

AU - Liss, Birgit

AU - Roeper, Jochen

PY - 2002/2/15

Y1 - 2002/2/15

N2 - Dopaminergic (DA) midbrain neurons in the substantia nigra (SN) and ventral tegmental area (VTA) are involved in various brain functions such as voluntary movement and reward and are targets in disorders such as Parkinson's disease and schizophrenia. To study the functional properties of identified DA neurons in mouse midbrain slices, we combined patch-clamp recordings with either neurobiotin cell-filling and triple labeling confocal immunohistochemistry, or single-cell RT-PCR. We discriminated four DA subpopulations based on anatomical and neurochemical differences: two calbindin D28-k (CB)-expressing DA populations in the substantia nigra (SN/CB+) or ventral tegmental area (VTA/CB+), and respectively, two calbindin D28-k negative DA populations (SN/CB-, VTA/CB-). VTA/CB+ DA neurons displayed significantly faster pacemaker frequencies with smaller afterhyperpolarizations compared with other DA neurons. In contrast, all four DA populations possessed significant differences in I(h) channel densities and I(h) channel-mediated functional properties like sag amplitudes and rebound delays in the following order: SN/CB- --> VTA/CB- --> SN/CB+ --> VTA/CB+. Single-cell RT-multiplex PCR experiments demonstrated that differential calbindin but not calretinin expression is associated with differential I(h) channel densities. Only in SN/CB- DA neurons, however, I(h) channels were actively involved in pacemaker frequency control. In conclusion, diversity within the DA system is not restricted to distinct axonal projections and differences in synaptic connectivity, but also involves differences in postsynaptic conductances between neurochemically and topographically distinct DA neurons.

AB - Dopaminergic (DA) midbrain neurons in the substantia nigra (SN) and ventral tegmental area (VTA) are involved in various brain functions such as voluntary movement and reward and are targets in disorders such as Parkinson's disease and schizophrenia. To study the functional properties of identified DA neurons in mouse midbrain slices, we combined patch-clamp recordings with either neurobiotin cell-filling and triple labeling confocal immunohistochemistry, or single-cell RT-PCR. We discriminated four DA subpopulations based on anatomical and neurochemical differences: two calbindin D28-k (CB)-expressing DA populations in the substantia nigra (SN/CB+) or ventral tegmental area (VTA/CB+), and respectively, two calbindin D28-k negative DA populations (SN/CB-, VTA/CB-). VTA/CB+ DA neurons displayed significantly faster pacemaker frequencies with smaller afterhyperpolarizations compared with other DA neurons. In contrast, all four DA populations possessed significant differences in I(h) channel densities and I(h) channel-mediated functional properties like sag amplitudes and rebound delays in the following order: SN/CB- --> VTA/CB- --> SN/CB+ --> VTA/CB+. Single-cell RT-multiplex PCR experiments demonstrated that differential calbindin but not calretinin expression is associated with differential I(h) channel densities. Only in SN/CB- DA neurons, however, I(h) channels were actively involved in pacemaker frequency control. In conclusion, diversity within the DA system is not restricted to distinct axonal projections and differences in synaptic connectivity, but also involves differences in postsynaptic conductances between neurochemically and topographically distinct DA neurons.

KW - Action Potentials

KW - Animals

KW - Biological Clocks

KW - Biotin

KW - Calbindin 2

KW - Calbindins

KW - Cyclic Nucleotide-Gated Cation Channels

KW - Dopamine

KW - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels

KW - Immunohistochemistry

KW - Ion Channels

KW - Membrane Potentials

KW - Mesencephalon

KW - Mice

KW - Mice, Inbred C57BL

KW - Nerve Tissue Proteins

KW - Neurons

KW - Patch-Clamp Techniques

KW - Potassium Channels

KW - Pyrimidines

KW - RNA, Messenger

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - S100 Calcium Binding Protein G

KW - Substantia Nigra

KW - Ventral Tegmental Area

M3 - SCORING: Journal article

C2 - 11850457

VL - 22

SP - 1290

EP - 1302

JO - J NEUROSCI

JF - J NEUROSCI

SN - 0270-6474

IS - 4

ER -