DENDRITIC EXCITABILITY IN SUBICULUM AFTER CANNABINOIDS

腹侧下托是大脑奖励和记忆回路中的一个关键结构，提供从海马体形成到中脑边缘多巴胺系统终端区域的综合信息。大麻素，CB1受体已知存在于腹侧下带（vSub）的锥体神经元内。此外，我已经获得的初步数据表明，vSub爆裂锥体神经元对CB1激动剂的反应是，爆裂诱导的ca2 +尖峰（宽低振幅尖峰）增强。我们假设这些Ca++尖峰是由cb1受体调节体细胞和根尖树突的外向电流引起的。树突具有电压激活的电导，这使得它们可以将轴突或体细胞发起的脉冲传播到它们的远端区域。我计划首先使用体细胞/树突的双全细胞记录来检测爆发向树突的反向传播，通过体细胞电极触发一次爆发，并比较沿着树突的不同近端和远端点的爆发强度。这将与树突Ca++成像相结合。我们的假设是，如果更多的瞬态（a型）K+电流存在于树突的远端隔室中，我们应该看到爆发强度的下降，然后确定向外K+电流的不均匀分布是否参与了反向传播的形成。然后我将测量CB1调制的突发反向传播和K+电流。我们的实验室已经报道了持续向外的K+电流（d型）控制CA1锥体神经元中Ca++峰的树突起始。在CA1锥体神经元中，树突a型K+通道的近端到远端梯度增加，我将在vSub锥体神经元中进行测试。最后，我将反复用大麻素治疗小鼠，以确定这是否会改变树突兴奋性，使用膜片钳和Ca++成像在不同的停药时间点。

The ventral subiculum is a critical structure in the brain's reward and memory circuitry providing integrated information from the hippocampal formation to the terminal regions of the mesolimbic dopamine system. Cannabinoid, CB1 receptors are known to be present within the pyramidal neurons of the ventral subiculum (vSub). Furthermore, I have obtained preliminary data indicating that vSub bursting pyramidal neurons respond to CB1 agonists with an enhancement in burst-induced Ca++spikes (broad low amplitude spikes). We hypothesize these Ca++ spikes to result from CB 1 receptor modulation of outward currents in the soma and apical dendrites. Dendrites have voltage-activated conductances which allows there o propagate axon or soma initiated bursts into their distal regions. I plan to first examine burst backpropagation into the dendrites using dual whole-cell somatic/dendritic recordings initiating a burst with the somatic electrode arid comparing the strength of the burst at different proximal and distal points along the dendrite. This will be combined with dendritic Ca++ imaging. Our hypothesis Is that if more transient (A-type) K+ currents exist in the distal compartments of the dendrite we should see a decrease in burst strength and then determine if a nonuniform distribution of outward K+ currents is involved in shaping the backpropagation. I will then measure CB1 modulation of the burst backpropagation and the K+ currents. Our lab has reported that sustained outward K+ currents (D-type) control the dendritic initiation of Ca++ spikes in CA1 pyramidal neurons. An increasing proximal-to- distal gradient of dendritic A-type K+ channels has been reported in CA1 pyramidal neurons and I will test for this in the vSub pyramidal neurons. Finally, I will repeatedly treat mice with cannabinoids to determine if this changes dendritic excitability using both patch-clamp and Ca++ imaging at different withdrawal time points.