Intracerebroventricular vasopressin produces noradrenergic β-receptor-dependent potentiation of the perforant path-evoked potential in the dentate gyrus in vivo

Dove, Christina (2008) Intracerebroventricular vasopressin produces noradrenergic β-receptor-dependent potentiation of the perforant path-evoked potential in the dentate gyrus in vivo. Masters thesis, Memorial University of Newfoundland.

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Abstract

Long-term potentiation of a synaptic and/or spike response, which is widely accepted as a model for neuronal plasticity, was initially elicited by high frequency stimulation in the hippocampus (Bliss and Lomo, 1973), but can also be induced by neuromodulators like norepinephrine (NE; Neuman and Harley, 1983; Walling and Harley, 2004). The neuropeptide vasopressin (AVP) (Chen et al, 1993; Chepkova et al, 2001; Dubrovsky et al, 2002; Dubrovsky et al, 2003) also produces enhancement of synaptic responses and has a role in promoting memory (Bohus et al, 1982). In vitro studies have shown NE plays a role in AVP-initiated increases in cyclic AMP (cAMP) (Brinton, 2000; Brinton, 1993). -- It has been proposed that NE, released into the dentate gyrus in vivo mediates AVP memory enhancement (Bohus et al, 1993). This thesis examined 1) the perforant path-dentate gyrus evoked response after intracerebroventricular (icv) AVP; 2) the β-adrenergic influence on perforant path AVP effects through the use of a double pipette procedure using the β-adrenergic antagonist, propranolol; and 3) further examined the pharmacology of the perforant path AVP response by the use of the V1a selective agonist DGAVP, an AVP fragment without peripheral effects, in the urethane anesthetized rat. -- In the first experiment, AVP (1 ng; icv) produced potentiation of perforant path population spike amplitude in 15/16 animals and of the EPSP slope in 11/16 animals. AVP significantly increased the population spike amplitude with a mean increase of 50% over baseline at 30 minutes after AVP. Individual animals showed increases of up to 100% at peak potentiation. The mean increase for EPSP slope was 21%) over baseline at 30 minutes after AVP. Those experiments followed beyond an hour (n=4) showed mean amplitude increases of 100% at 60 minutes and mean slope increases of 24% at 60 minutes. At 100 minutes post AVP, mean spike amplitude was at a 90%) increase with the EPSP slope at a 16% increase above baseline. -- In the second experiment using a two-pipette recording technique, perforant path evoked potentials were recorded using a β-adrenergic antagonist (propranolol)-filled pipette and a saline-filled pipette before and after icv AVP. AVP produced a mean increase of 50% of the baseline population spike amplitude in all 6 animals on the saline pipette at 30 minutes after AVP. AVP also produced potentiation of the EPSP slope on the saline pipette in all animals with a mean increase of 25% at 30 minutes after AVP infusion. With the propranolol pipette at 30 minutes all 6 animals showed an unchanged or decreased population spike amplitude averaging 21% of baseline and a decreased EPSP slope averaging 26% of baseline. -- In the final experiment, the AVP fragment, DGAVP increased in the population spike amplitude in 3 animals with a mean amplitude of 100% above baseline at 30 minutes which remained constant at 60 minutes. DGAVP did not significantly alter EPSP slope. -- Taken together, the results of these experiments demonstrate that AVP produces long-lasting potentiation of the perforant path evoked potential in vivo in the dentate gyrus, without tetanic stimulation. This confirms in vitro experiments on the effects of AVP on the perforant path evoked potential. The dependence of AVP-induced electrophysiological potentiation on NE receptor mediation in the dentate gyrus parallels the results obtained with AVP-infusion in the dentate gyrus in vivo on the potentiation of avoidance memory and with in vitro effects of AVP potentiation of NE-mediated cAMP production.

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