[Dopamine-dependent long-term depression in hippocampus of rat induced by exposure to spatial novelty.]

To study the role of long-term depression (LTD) in the mechanisms of learning and memory in hippocampus of rat, recordings were taken from freely moving animals that had undergone chronic implantation of a recording electrode in the hippocampus CA1 region and a bipolar stimulating electrode in the ipsilateral Schaffer collateral-commissural pathway. The recording electrode was inserted 3.8 mm posterior to bregma and 2.8 mm right of the midline, and the stimulating electrode was inserted 4.8 mm posterior to bregma and 3.8 mm right of the midline via holes drilled through the skull. The entire assembly was connected with a rubber socket on the animal's head and then stabilized with dental cement. The correct placement of the electrodes into the hippocampal CA1 area was confirmed via electrophysiological criteria and postmortem histological analysis. After 2 weeks of surgery recovery, the rats were placed in the familiar recording chamber for 3 days. The field excitatory postsynaptic potentials (fEPSPs) were evoked by stimulating with a square wave constant current pulse of 0.2 ms duration, at a frequency of 0.033 Hz and at a stimulation intensity adjusted to given an fEPSP amplitude of 50% of the maximum, and the baseline of fEPSPs were recorded for 3 days in the familiar recording environment at the same time each day. A novelty environment that was made of clear Perspex (40 cm x 40 cm x 40 cm) was prepared and we examined whether exposure to a novelty spatial environment facilitated the expression of activity-dependent persistent decrease in synaptic transmission (namely LTD) at CA1 synapses in the rat hippocampus. The results showed that brief exposure to a novelty environment for 10 min facilitated the expression of LTD in the hippocampal CA1 area under no other exogenous high- or low-frequency stimulation protocol. This facilitatory effect was dependent on the activation of D1/D5 receptors: the D1/D5 receptors antagonist SCH23390 prevented the decrease of synaptic transmission in the hippocampus during the novelty exploration. These data provided important evidence that LTD may underlie certain forms of learning and memory and that dopamine participates in the synaptic plasticity in the process of hippocampal spatial information storage.