Carbachol-induced NMDA-independent complex bursting of midbrain dopaminergic neurons – in vivo electrophysiological and pharmacological studies on NR1DATCreERTt2 mice

• Autorzy: Walczak M. , Szumiec L. , Rodriguez Parkitna J. , Blasiak T.
• Języki publikacji: EN

Abstrakty

EN

Dopamine plays a key role in the control of behaviour and motor functions. The amount of neurotransmitterreleased into a synapse depends on the firing pattern of dopaminergic neurons, which occurs as a continuum be‑ tween regular and bursting modes of activity. The latter mode results in a phasic increase of dopamine release, whereas a basal level of neurotransmitter is maintained by non-bursting (tonic or irregular) firing of dopaminergic neurons. While functional NMDA receptors are considered crucial for evoking dopaminergic neurons’ bursts of ac‑ tion potentials, it remains an open question whether other neurotransmitters also evoke this type of activity. There‑ fore, the aim of our research was to determine the effect of cholinergic receptor stimulation on the activity of dopa‑ mine neurons lacking functional NMDA receptor. We used a genetically modified strain of mice (NR1DATCreERT2), which allowed us to induce a deletion of the NR1 NMDA receptor subunit selectively on dopaminergic neurons of adult animals. Experiments were performed on urethane anaesthetised animals. We used multi-barrel glass micro‑ pipettes (five barrels), allowing us to combine single unit extracellular recordings of midbrain dopaminergic neu‑ rons’ activity and iontophoresis, local application of drugs (a nonspecific agonist of cholinergic receptors – carbachol; muscarinic and nicotinic receptor antagonists – scopol‑ amine and mecamylamine, respectively; and NMDA). Loss of NMDA receptors on dopaminergic neurons decreased their basal firing rate, attenuated bursting, and abolished responsivity to NMDA compared to wild-type animals. Af‑ ter application of carbachol, the vast majority of dopami‑ nergic neurons increased their firing rate. Interestingly, some of the recorded cells, both in control and NR1DAT‑ CreERT2 mice, developed slow oscillatory changes in firing rate, which transformed into robust complex bursts of ac‑ tion potentials. These results show that agonists of cholin‑ ergic receptors can modulate rate as well as pattern of fir‑ ing of the midbrain dopaminergic neurons. Furthermore, our observations suggest that activation of cholinergic re‑ ceptors alone, i.e. without the involvement of NMDA recep‑ tors, can switch a subpopulation of dopaminergic neurons to a burst firing mode. Funding: NCN, Poland, PRELUDIUM 2015/19/N/NZ4/00960.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2018
• Tom: 78
• Numer: Suppl.1
• Opis fizyczny: p.11

Twórcy

autor

Walczak M.

• Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland

autor

Szumiec L.

• Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Rodriguez Parkitna J.

• Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Blasiak T.

• Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland