Neuregulin-1beta modulates in vivo entorhinal-hippocampal synaptic transmission in adult rats.

ABSTRACT

Neuregulin-1 (NRG-1) proteins and their erbB receptors are essential for neuronal development during embryogenesis and may contribute importantly to neuronal function in the adult brain. This study tests the hypothesis that NRG-1beta acts as a modulator of synaptic activity in the adult brain, specifically at hippocampal formation synapses. Adult, male Sprague-Dawley rats were anesthetized and a recording electrode with an attached stainless steel microinjector was stereotaxically positioned to record field potentials (fEPSP) in either the dentate gyrus or the cornu ammonis (CA) 1 field of the hippocampus. The entorhinal cortex was continuously stimulated via a paired stainless steel electrode. Microinjection of NRG-1beta significantly increased the slope of the fEPSP in the dentate gyrus in a dose-dependent manner. Compared with a low dose (20 nM), a high dose (100 nM) of NRG-1beta induced a shorter latency response that was of greater magnitude. Responses to NRG-1beta were abolished by pretreatment with a selective, reversible erbB tyrosine kinase inhibitor, PD158780 (100 microM). Further, PD158780 (100 microM) itself significantly decreased the entorhinal-dentate fESPS slope by about 15%. Neither equimolar (100 nM) nor hypermolar (100 microM) sucrose or heat-inactivated NRG-1beta (100 nM) significantly altered the entorhinal-dentate fEPSP slope. In contrast to its effect at the entorhinal-dentate synapse, NRG-1beta (100 nM) depressed, and PD158780 potentiated entorhinal-CA1 synaptic transmission. Thus, in adult rats NRG-1beta potentiates transmission at the entorhinal-dentate synapse but suppresses transmission at the entorhinal-CA1 synapse. These observations indicate that NRG-1 is not only a developmental growth factor, but also modifies synaptic transmission in adult rat brain.