Neurotensin depolarizes cholinergic and a subset of non-cholinergic septal/diagonal band neurons by stimulating neurotensin-1 receptors
Section snippets
In vitro slice preparation
Preparation of brain slices for electrophysiological recordings was done as described previously.17., 33. In brief, male and female albino guinea-pigs (Harlan Sprague–Dawley) weighing 200–400 g were decapitated, and the brain was quickly removed and placed in ice-cold oxygenated physiological solution. The forebrain was trimmed with a razor blade and fixed to a vibrating tissue slicer chuck with cyanoacrylate glue. Coronal slices of the forebrain (400–500 μm) were cut 0.5–2 mm anterior to the
Effects of neurotensin on membrane potential and membrane resistance
A sample of 47 MS/vDB neurons was recorded in slices of guinea-pig forebrain. Twenty-five neurons were classified as cholinergic neurons based upon previously established electrophysiological characteristics.17., 18., 19. Twenty-two neurons were classified as non-cholinergic, fast afterhyperpolarization (fast AHP) type neurons. A third type of MS/vDB neuron, a burst-firing type neuron, was found too infrequently to be included in this study. Table 1 summarizes some of the active and passive
Increase in cholinergic neuron excitability: likely mechanisms
Data presented here suggest that NT induces a slow depolarization of cholinergic MS/vDB neurons. Depolarization was accompanied by a small increase in membrane resistance in most neurons, and a decrease in the Ca2+-dependent K+ current that is responsible for the long component of the post-spike AHP (long AHP). The long AHP is most probably the apamin-insensitive AHP that has been seen after single spikes or spike trains in these and other neurons.33., 44., 47. The long AHP in MS/vDB neurons
Conclusions
NT was found to have multiple effects on cholinergic and non-cholinergic MS/vDB neurons that together resulted in a slow depolarization, reduced post-spike AHPs and enhanced excitability. Cholinergic neurons with a sufficiently large low-voltage-activated calcium current could be induced to fire in bursts. The actions of NT appear to be mediated by NT-1 receptors. Selective stimulation of basal forebrain NT-1 receptors may hold promise for increasing cortical cholinergic tone in diseases such
Acknowledgments
This work was supported by an MBRS research grant from NIH (GM0803; J. G. Townsel, administrative P.I.) and by an HBCU research grant supplement from NIH (DA05255; C. Napier, P.I.).
References (56)
- et al.
Characterization of binding sites of a new neurotensin receptor antagonist, [3H]SR 142948A, in the rat brain
Eur. J. Pharmac.
(1998) - et al.
Extrinsic and intrinsic properties underlying oscillation and synchrony in limbic cortex
Prog. Neurobiol.
(1993) - et al.
Theta burst stimulation is optimal for induction of LTP at both apical and basal dendritic synapses on hippocampal CA1 neurons
Brain Res.
(1992) - et al.
Molecular cloning of a levocabastine-sensitive neurotensin binding site
Fedn Eur. biochem. Socs Lett.
(1996) - et al.
Priming of associative long-term depression in the dentate gyrus by θ frequency synaptic activity
Neuron
(1992) The organization and some projections of cholinergic neurons of the mammalian forebrain
Brain Res. Rev.
(1982)- et al.
Electrophysiology of AChE-positive neurons in basal forebrain slices
Neurosci. Lett.
(1986) - et al.
Cholinergic nucleus basalis neurons display the capacity for rhythmic bursting activity mediated by low-threshold calcium spikes
Neuroscience
(1992) - et al.
A comparison of extracellular and intracellular recordings from medial septal/diagonal band neurons in vitro
Neuroscience
(1991) - et al.
Neurotensin induces an inward current in rat mesencephalic dopaminergic neurons
Neurosci. Lett.
(1993)