Long-term potentiation in the dentate gyrus in freely moving rats is reinforced by intraventricular application of norepinephrine, but not oxotremorine.

Growing evidence suggests that processes of synaptic plasticity, such as long-term potentiation (LTP) occurring in one synaptic population, can be modulated by consolidating afferents from other brain structures. We have previously shown that an early-LTP lasting less than 4 h (E-LTP) in the dentate gyrus can be prolonged by stimulating the basolateral amygdala, the septum or the locus coeruleus within a specific time window. Pharmacological experiments have suggested that noradregeneric (NE) and/or cholinergic systems might be involved in these effects. We have therefore investigated whether the direct intraventricular application of agonists for NE- or muscarinic receptors is able to modulate synaptic plasticity. E-LTP was induced at the dentate gyrus of freely moving rats using a mild tetanization protocol that induces only an E-LTP. NE or oxotremorine (OXO) were applied icv 10 min after the tetanus. Results show that low doses of NE (1.5 and 5 nM) effectively prolong LTP. A higher dose (50 nM) was not effective. None of the OXO doses employed (5, 25, and 50 nM) showed similar effects. These results stress the importance of transmitter-specific modulatory influences on the time course of synaptic plasticity, in particular NE whose application mimics the reinforcing effect of directly stimulating limbic structures on LTP.