title: Dopamine D1/5 receptor modulation of firing rate and bidirectional theta burst firing in medial septal/vertical limb of diagonal band neurons in vivo.
abstract: The medial septum/vertical limb of diagonal band complex (MS/vDB) consists of cholinergic, GABAergic, and glutamatergic neurons that project to the hippocampus and functionally regulate attention, memory, and cognitive processes. Using tyrosine hydroxlase (TH) immunocytochemistry and dark-field light microscopy, we found that the MS/vDB is innervated by a sparse network of TH-immunoreactive (putative catecholaminergic) terminals. MS/vDB neurons are known to fire in rhythmic theta burst frequency of 3-7 Hz to pace hippocampal theta rhythm. Extracellular single-unit recording in theta and non-theta firing MS/vDB neurons and antidromically identified MS/vDB-hippocampal neurons were made in urethan-anesthetized rats. Tail-pinch noxious stimuli and ventral tegmental area (VTA) stimulation (20 Hz) evoked spontaneous theta burst firing in MS/vDB neurons. Systemic D1/5 antagonists SCH23390 or SCH39166 (0.1 mg/kg iv) alone suppressed the spontaneous theta bursts, suggesting a tonic facilitatory endogenous dopamine D1 "tone" that modulates theta bursts in vivo. Activation of D1/5 receptor by dihydrexidine (10 mg/kg iv) led to an increase in mean firing rate in 60% of all theta and non-theta MS/vDB neurons with an increase in the number of theta bursts and spikes/burst in theta cells. In strong theta firing MS/vDB neurons, D1/5 receptor stimulation suppressed the occurrence of theta burst firing, whereas the overall increase in spontaneous mean firing rate remained. In low baseline theta MS/vDB neurons D1/5 receptor stimulation increases the occurrence of theta bursts along with a net increase in mean firing rate. Atropine injection consistently disrupts theta burst pattern and reduced the time spent in theta firing. Collectively, these data suggest that dopamine D1/5 stimulation enhances the mean firing rate of most MS/vDB neurons and also provides a state-dependent bidirectional modulation of theta burst occurrence. Some of these MS/vDB neurons may be cholinergic or GABAergic that may indirectly regulate theta rhythm in the hippocampus.
authors.affiliation: Neuroscience Discovery, Eli Lilly & Co., Lilly Corporate Ctr., Indianapolis, IN 46285-0510, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Fitch
authors.forename: Robert N
authors.initials: RN
authors.lastname: Sahr
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Eastwood
authors.forename: Feng C
authors.initials: FC
authors.lastname: Zhou
authors.forename: Charles R
authors.initials: CR
authors.lastname: Yang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010617:Phenanthridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D050641:Receptors, Dopamine D5 / Q000502:physiology*; D012686:Septal Nuclei / Q000166:cytology*; D013826:Theta Rhythm; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018727:Muscarinic Antagonists; D010617:Phenanthridines; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; C061532:dihydrexidine; D001285:Atropine; D014446:Tyrosine 3-Monooxygenase; D000109:Acetylcholine