Intrinsic excitability of cholinergic neurons in the rat parabigeminal nucleus.
Cholinergic neurons in the parabigeminal nucleus of the rat midbrain were studied in an acute slice preparation. Spontaneous, regular action potentials were observed both with cell-attached patch recordings as well as with whole cell current-clamp recordings. The spontaneous activity of parabigeminal nucleus (PBN) neurons was not due to synaptic input as it persisted in the presence of the pan-ionotropic excitatory neurotransmitter receptor blocker, kynurenic acid, and the cholinergic blockers dihydro-beta-erythroidine (DHbetaE) and atropine. This result suggests the existence of intrinsic currents that enable spontaneous activity. In voltage-clamp recordings, I(H) and I(A) currents were observed in most PBN neurons. I(A) had voltage-dependent features that would permit it to contribute to spontaneous firing. In contrast, I(H) was significantly activated at membrane potentials lower than the trough of the spike afterhyperpolarization, suggesting that I(H) does not contribute to spontaneous firing of PBN neurons. Consistent with this interpretation, application of 25 microM ZD-7288, which blocked I(H), did not affect the rate of spontaneous firing in PBN neurons. Counterparts to I(A) and I(H) were observed in current-clamp recordings: I(A) was reflected as a slow voltage ramp observed between action potentials and on release from hyperpolarization, and I(H) was reflected as a depolarizing sag often accompanied by rebound spikes in response to hyperpolarizing current injections. In response to depolarizing current injections, PBN neurons fired at high frequencies, with relatively little accommodation. Ultimately, the spontaneous activity in PBN neurons could be used to modulate cholinergic drive in the superior colliculus in either positive or negative directions.
Goddard
C Alex
CA
Department of Neurobiology, Stanford University, Stanford, CA, 94305, USA. cgoddard@stanford.edu
Knudsen
Eric I
EI
Huguenard
John R
JR
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D007736:Kynurenic Acid / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology* / Q000502:physiology*; D008839:Microelectrodes; D009415:Nerve Net / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000166:cytology* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013477:Superior Colliculi / Q000166:cytology / Q000502:physiology; D013569:Synapses / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D011743:Pyrimidines; C082246:ICI D2788; D007736:Kynurenic Acid