DENDRITIC EXCITABILITY IN SUBICULUM AFTER CANNABINOIDS

腹侧下丘是大脑奖赏和记忆回路中的一个关键结构，提供从海马结构到中脑边缘多巴胺系统终末区域的综合信息。已知大麻素CB1受体存在于腹侧下丘(VSub)的锥体神经元内。此外，我已经获得了初步数据，表明vSub爆发的锥体神经元对CB1激动剂的反应是通过增强爆发诱导的钙尖峰(宽而低幅度的尖峰)。我们推测这些Ca++峰可能是由于Cb1受体对胞体和顶端树突外向电流的调节所致。树突具有电压激活的电导，这允许轴突或胞体发起的爆发传播到它们的远端区域。我计划首先使用两个全细胞体细胞/树突记录来研究猝发向树突的反向传播，用体细胞电极发起猝发，并比较沿着树突的不同近端和远端爆发点的强度。这将与树突状钙离子成像相结合。我们的假设是，如果在树突的远端隔室存在更多的瞬时(A型)K+电流，我们应该会看到爆发强度的下降，然后确定外向K+电流的不均匀分布是否参与了反向传播的形成。然后，我将测量突发反向传播和K+电流的CB1调制。本实验室已报道持续外向K+电流(D型)控制CA1区锥体神经元中钙离子刺激峰的树突起始。据报道，在CA1锥体神经元中，树突状A型K+通道的近端到远端的梯度增加，我将在vSub锥体神经元中测试这一点。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状细胞的兴奋性，在不同的戒断时间点使用膜片钳和钙离子成像。

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.