Membrane and morphological properties in medium spiny neurons of dorsal striatum in Akt1 knockout mice.

• Main Authors: Hui-Yun Kau, 高慧芸
• Other Authors: Ming-Yuan Min
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/71960959257572966323

碩士 === 臺灣大學 === 動物學研究所 === 98 === AKT, also known as Protein Kinas B, plays many important roles in regulation of neuronal growth in the central nervous system. Recent evidence has shown that there is a decreased AKT1 protein level in schizophrenia patients, suggesting that it might be one of the susceptibility genes for schizophrenia. However, the direct impact of AKT1 dysfunction on the neuronal function is poorly understood. In the present study, the physiological and morphological properties of medium spiny neurons (MSN) in the striatum were compared among wild-type (WT), Akt1-heterozyous (Akt1 -/+) and Akt1 knockout (Akt1-/-) mice. The MSNs were characterized by the presence of large number of dendritic spines and having relatively hyperpolarized resting membrane potential (~ -80 mV). The intrinsic membrane properties and excitability of MSN were firstly examined. The input resistance (Rn) of MSN in Akt1-/- was significantly higher than that in WT mice, while the rheobase (Rh) was remarkably lower in Akt1-/- than in WT mice. As for the input-output (I/O) relationship, defined as the intensity of injected depolarizing current versus the resulted instantaneous firing frequency, no significant difference in the gain was found between WT and Akt1-/- mice, though significant left-shifting of the I/O relationship was observe in Akt1-/- mice, which may be attributed to the lower Rh of MSN in Akt1-/- mice. In addition, lower number of primary dendrites and lower complexity of dendrites were observed in Akt1-/- mice. These morphological changes indicate that AKT dysfunction impairs the growth of dendritic trees in early neuronal development and leads to alter membrane properties such as higher Rn and lower Rh in MSNs in Akt1 -/- mice. With regard to the excitatory and inhibitory neurotransmission, there were no significant differences of excitatory neurotransmission in efficacy of transmitter release and overall property at synaptic sites between WT and Akt1 -/- mice, however Akt deficit affected inhibitory neurotransmission at both pre- and post-synaptic sites. Data from the LTD of corticotriatal pathway in MSNs showed a requirement for D2 receptor activation. Blockade of AKT signaling did not elicit the formation of LTD, which indicates AKT signaling may be involved in this form of LTD.