Klinische Neurophysiologie 2013; 44 - P134
DOI: 10.1055/s-0033-1337275

Reduced threshold for induction of LTP by phasic activation of dopamine D1/D5 receptors at hippocampal CA1-subiculum synapses

E Roggenhofer 1, 2, P Fidzinski 2, 3, O Shor 2, 3, J Behr 2, 3
  • 1Max Planck Institute for Human Cognitive and Brain Sciences, Neurology, Leipzig, Deutschland
  • 2Charite – Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Berlin, Deutschland
  • 3Charite – Universitätsmedizin Berlin, Institute for Neurophysiology, Berlin, Deutschland

Introduction:

The phasic release of dopamine in the hippocampal formation has been shown to facilitate the encoding of novel information. There is evidence that the subiculum operates as a detector and distributor of sensory information which incorporates the novelty and relevance of signals received from CA1. The subiculum acts as the final hippocampal relay station for outgoing information. Subicular pyramidal cells have been classified as regular- and burst-spiking neurons. The goal of the present study was to study the effect of dopamine D1/D5-receptor activation on synaptic transmission and long-term potentiation (LTP) in subicular regular-spiking neurons.

Methods:

Intracellular recordings with sharp microelectrode and patch-clamp technique were performed in subicular regular-spiking cells of 4 – 6 week old Wistar rats using a high-frequency stimulation protocol set at a level subthreshold for LTP induction. After prior activation of D1/D5-receptors (D1/D5-receptor agonist SKF 38393, 100µM), we investigated the effect of NMDA-receptor blockade (D-APV, 100µM), protein kinase A inhibition (H-89, 10µM) and application of an intracellular Ca2+ chelator (BAPTA, 30 mM) on LTP induction.

Results:

We demonstrate that priming stimulation of D1/D5-receptors reduces the threshold for the induction of LTP in subicular regular-spiking neurons. Our results indicate that phasic D1/D5-receptor activation facilitates a postsynaptic form of LTP in subicular regular-spiking cells that is NMDA-R-dependent, relies on postsynaptic Ca2+ signaling and requires the activation of protein kinase A.

Discussion:

Subicular regular-spiking cells might be regulated and modulated by phasic dopaminergic and glutamatergic inputs to provide differenzial processing of novel and familiar sensory information from the hippocampus to different cortical and subcortical brain regions. The enhanced propensity of subicular regular-spiking cells to express postsynaptic LTP after activation of D1/D5-receptors can provide an intriguing mechanism for the selective encoding of hippocampal output information.