TY  - GEN
N2  - Dopamine (DA) is the predominant catecholamine neurotransmitter in the mammalian brain, where DA governs a variety of functions including locomotor activity, cognition, emotion, synaptic plasticity, learning and memory formation. In the hippocampus, activation of D1/5 receptors (D1/5Rs) is known to stabilize memory formation and late, protein-dependent long-term potentiation (LTP) in the stratum radiatum (RAD), whereas activation of D4 receptors (D4Rs) inhibits early LTP in the stratum oriens (OR) and depotentiates LTP in RAD. Interestingly, novelty exploration rescues memory impairment caused by blockade of D1/5Rs in the hippocampus. However, the function of D4Rs in synaptic plasticity, neural network activity and memory-associated behaviors remained to be elucidated in vivo. I implanted two recording electrodes targeting OR and RAD together with a bipolar stimulation electrode placed either in OR or RAD while monitoring depth profiles of stimulus-evoked local field potentials (eLFPs). At least one week later, eLFPs and spontaneous oscillatory activities (sLFPs) were recorded in the hippocampus of freely behaving mice to investigate the role of D4Rs under physiological condition. My results show that systemic, intraperitoneal treatment with the D4R agonist PD 168077 (PD) slightly decreased eLFPs both in OR and RAD and in parallel increased the paired-pulse ratio (PPR) between two eLFPs, indicating presynaptic mechanisms were involved in this modulation. PD treatment postponed the rapid eye movement (REM) sleep and, during REM onset, the theta peak frequency was shifted to lower band, the gamma band power was reduced and the strength of theta-gamma coupling was attenuated. Furthermore, D4R agonist treatment impaired late LTP (4 hours) both in OR and RAD, while early LTP (30 min) was reduced only in OR. When mice were transferred from their home cage to a fear box, band power of fast gamma increased in that novel environment, in particular after receiving an electric footshock on day 1 and during context exposure on day 2, and these increases persisted when the mice were returned to home cage immediately after. These changing patterns of oscillatory activities were not affected by PD treatment, and therefore the D4R-mediated layer-specific modulation of synaptic plasticity in the hippocampus is unlikely implicated in learning and memory during novelty exploration or fear conditioning.
A1  - Li, Shi-Bin
AV  - public
TI  - D4 Dopamine Receptor-Mediated Modulation of Hippocampal Synaptic Efficacy and Network Activity in Behaving Mice
ID  - heidok17165
Y1  - 2014///
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/17165/
ER  -