Abstract
To determine how norepinephrine affects the basic physiological properties of catecholaminergic neurons, brain slices containing the substantia nigra pars compacta and locus coeruleus were studied with cell-attached and whole-cell recordings in control and dopamine β-hydroxylase knockout (Dbh -/-) mice that lack norepinephrine. In the cell-attached configuration, the spontaneous firing rate and pattern of locus coeruleus neurons recorded from Dbh -/- mice were the same as the firing rate and pattern recorded from heterozygous littermates (Dbh +/-). During whole-cell recordings, synaptic stimulation produced an α-2 receptor-mediated outward current in the locus coeruleus of control mice that was absent in Dbh -/- mice. Normal α-2 mediated outward currents were restored in Dbh -/- slices after pre-incubation with norepinephrine. Locus coeruleus neurons also displayed similar changes in holding current in response to bath application of norepinephrine, UK 14304, and methionine-enkephalin. Dopamine neurons recorded in the substantia nigra pars compacta similarly showed no differences between slices harvested from Dbh -/- and control mice. These results indicate that endogenous norepinephrine is not necessary for the expression of catecholaminergic neuron firing properties or responses to direct agonists, but is necessary for auto-inhibition mediated by indirect α-2 receptor stimulation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1067-1074 |
| Number of pages | 8 |
| Journal | Neuroscience |
| Volume | 144 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 9 2007 |
| Externally published | Yes |
Keywords
- cocaine
- dopamine β-hydroxylase knockout
- locus coeruleus
- substantia nigra pars compacta
ASJC Scopus subject areas
- Neuroscience(all)