DENDRITIC EXCITABILITY IN SUBICULUM AFTER CANNABINOIDS

腹侧下托是大脑奖赏和记忆回路中的关键结构，提供从海马结构到中脑边缘多巴胺系统末端区域的整合信息。 已知大麻素CB 1受体存在于腹侧下托（vSub）的锥体神经元内。 此外，我已经获得的初步数据表明，vSub爆发锥体神经元响应CB 1激动剂与增强爆发诱导的Ca++尖峰（宽低幅度尖峰）。 我们假设这些Ca++尖峰是由于CB 1受体对索马和顶树突外向电流的调节。 树突具有电压激活的电导，其允许轴突或索马引发的爆发在其远端区域中传播。 我计划首先使用双全细胞体细胞/树突记录来检查到树突的爆发反向传播，用体细胞电极启动爆发，并比较沿着树突的不同近端和远端点处的爆发强度。 这将与树突状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室中，我们应该看到爆裂强度的下降，然后确定向外的K+电流的不均匀分布是否参与形成反向传播。然后，我将测量CB 1对突发反向传播和K+电流的调制。 本实验室报道了持续外向K+电流（D型）控制CA 1锥体神经元树突状细胞Ca++峰的起始。 据报道，在CA 1锥体神经元中，树突状A型K+通道的近端到远端梯度增加，我将在vSub锥体神经元中对此进行测试。 最后，我将反复用大麻素治疗小鼠，以确定这是否会在不同的戒断时间点使用膜片钳和Ca++成像来改变树突的兴奋性。

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.