Neurotensin depolarizes cholinergic and a subset of non-cholinergic septal/diagonal band neurons by stimulating neurotensin-1 receptors

Identified cholinergic and a subtype of non-cholinergic, fast-firing. neuro ns were recorded intracellularly in vitro from slices of guinea-pig brain. Recorded neurons were within the boundaries of the medial septum and vertic al limb of the diagonal band of the forebrain. The effects of superfused ne urotensin and neurotensin receptor antagonists were measured under single-e lectrode current clamp. Neurotensin consistently caused a dose-dependent, s low depolarization of cholinergic neurons that was accompanied by an increa se in membrane resistance and a block of the long-duration (1-10 s) post-sp ike afterhyperpolarization when present. Neurotensin also blocked a shorter duration, slow afterhyperpolarization, but only in a minority of cholinerg ic neurons. When present, inhibition of the slow afterhyperpolarization cha nged the spike pattern from single spikes to short bursts. Inhibition of po st-spike afterhyperpolarizations by neurotensin reversed more slowly than d id other effects of neurotensin. Tetrodotoxin did not prevent the depolariz ing effect of neurotensin. The non-selective neurotensin receptor antagonis t, SR142948A, blocked the depolarizing effect of neurotensin but the low-af finity receptor antagonist, levocabastine, did not. A subgroup of noncholin ergic, fast-firing neurons (23%) was also depolarized by neurotensin, an ef fect antagonized by SR142948A but not levocabastine. Neurotensin did not ef fect post-spike voltage transients or change the firing pattern of non-chol inergic neurons. These data suggest that neurotensin causes a slow depolarization and increa sed excitability of cholinergic and some noncholinergic neurons in an area of the brain that projects to the hippocampus. Neurotensin type 1 receptors appear to mediate these effects. Neurotensin may modulate hippocampal-depe ndent learning and memory processes through its effects on septohippocampal neurons. (C) 1999 IBRO. Published by Elsevier Science Ltd.