AN ACTIVE MEMBRANE MODEL OF THE CEREBELLAR PURKINJE-CELL .2. SIMULATION OF SYNAPTIC RESPONSES
AN ACTIVE MEMBRANE MODEL OF THE CEREBELLAR PURKINJE-CELL .2. SIMULATION OF SYNAPTIC RESPONSES
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DOI：
10.1152/jn.1994.71.1.401
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发表时间：
1994-01-01
影响因子：
2.5
通讯作者：
BOWER, JM
中科院分区：
文献类型：
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作者：
DESCHUTTER, E;BOWER, JM
1.兴奋性和抑制性突触后通道被添加到先前描述的复杂的小脑浦肯野细胞的房室模型，以检查模型对突触输入的反应。所有模型参数保持如前所述，留下最大突触电导作为本文所述研究中调整的唯一参数。在这些条件下，该模型能够再现对每种主要类型的突触输入的生理记录响应。2.当兴奋性突触被激活的光滑树突的模型，该模型产生了一个复杂的树突状Ca 2+尖峰类似于攀爬纤维输入所产生的。检查模型表明，激活的P-型Ca 2+通道的光滑和多刺树突增强的去极化过程中复杂的穗和Ca 2+激活的K+通道在相同的树突区域确定的穗的持续时间。当这些突触在模拟电流钳条件下被激活时，该模型也产生了复杂锋电位的特征性双反转电位。树突状复合体尖峰的形状可以通过改变攀爬纤维突触的最大电导来改变，从而改变进入细胞的Ca 2+的量。3.为了探索浦肯野细胞在体内的背景简单尖峰放电特性，我们在模型的多刺树突分支中加入了兴奋性“平行纤维”突触。这些颗粒细胞突触的连续异步激活导致自发钠峰的产生。然而，非常低的异步输入频率产生了高度规则的，非常快的节奏（80-120 Hz），而稍高的输入频率导致浦肯野细胞爆裂。这两种类型的活动是不典型的体内浦肯野细胞记录。4.这种抑制性突触可能是由星状细胞产生的，也被添加到树突树中。当这些抑制性突触的异步激活与连续的异步兴奋性输入相结合时，该模型以真实的浦肯野细胞典型的更随机的模式产生躯体动作电位。在这些条件下，模拟interspike间隔分布类似于实验记录中发现的。此外，与体内记录一样，该模型没有产生树突状爆发。这主要是由于抑制了树突状细胞Ca 2+峰的产生。5.在异步抑制的存在下，兴奋性输入的平均频率的变化调制的背景简单的尖峰放电频率在自然范围内的浦肯野细胞放电频率（30-100 Hz）。这种调制对兴奋性输入的平均频率的微小变化非常敏感。此外，抑制频率的变化引起兴奋性输入和尖峰频率之间的关系的平行移动。由于特定的小脑回路，抑制性输入可以允许浦肯野细胞在任何平均输入频率下检测兴奋性输入的小波动。6.在背景非同步兴奋性和抑制性输入同时给予攀爬纤维输入时，索马复合峰的形状受到显着影响。而树突内峰电位的形状几乎不变，这种差异反映了索马的兴奋性较树突更易变化。7.在颗粒和星状细胞突触的异步激活期间，篮状细胞抑制性突触的同步激活中断了躯体尖峰。然而，由篮状细胞突触引起的超极化并没有深入到树突，而是停留在索马和主树突。8.这项模拟工作表明，电压钳数据的基础上，完全调整的浦肯野细胞电流注入的反应模型是能够再现范围广泛的突触激活的反应。在连续颗粒细胞兴奋的存在下，该模型显示出不同于沉默的、静止的体外状态的稳定的体内状态。此外，该模型表明，不同类型的突触输入之间可能存在重要的功能相互作用。特别是，它对星状细胞抑制的作用做出了几个具体的预测。
1. Both excitatory and inhibitory postsynaptic channels were added to a previously described complex compartmental model of a cerebellar Purkinje cell to examine model responses to synaptic inputs. All model parameters remained as described previously, leaving maximum synaptic conductance as the only parameter that was tuned in the studies described in this paper. Under these conditions the model was capable of reproducing physiological recorded responses to each of the major types of synaptic input. 2. When excitatory synapses were activated on the smooth dendrites of the model, the model generated a complex dendritic Ca2+ spike similar to that generated by climbing fiber inputs. Examination of the model showed that activation of P-type Ca2+ channels in both the smooth and spiny dendrites augmented the depolarization during the complex spike and that Ca2+-activated K+ channels in the same dendritic regions determined the duration of the spike. When these synapses were activated under simulated current-clamp conditions the model also generated the characteristic dual reversal potential of the complex spike. The shape of the dendritic complex spike could be altered by changing the maximum conductance of the climbing fiber synapse and thus the amount of Ca2+ entering the cell. 3. To explore the background simple spike firing properties of Purkinje cells in vivo we added excitatory ''parallel fiber'' synapses to the spiny dendritic branches of the model. Continuous asynchronous activation of these granule cell synapses resulted in the generation of spontaneous sodium spikes. However, very low asynchronous input frequencies produced a highly regular, very fast rhythm(80-120 Hz), whereas slightly higher input frequencies resulted in Purkinje cell bursting. Both types of activity are uncharacteristic of in vivo Purkinje cell recordings. 4. Inhibitory synapses of the sort presumably generated by stellate cells were also added to the dendritic tree. When asynchronous activation of these inhibitory synapses was combined with continuous asynchronous excitatory input the model generated somatic action potentials in a much more stochastic pattern typical of real Purkinje cells. Under these conditions simulated interspike interval distributions resembled those found in experimental recordings. Also, as with in vivo recordings, the model did not generate dendritic bursts. This was mainly due to inhibition that suppressed the generation of dendritic Ca2+ spikes. 5. In the presence of asynchronous inhibition, changes in the average frequency of excitatory inputs modulated background simple spike firing frequencies in the natural range of Purkinje cell firing frequencies( 30-100 Hz). This modulation was very sensitive to small changes in the average frequency of excitatory inputs. In addition, changes in inhibitory frequency caused a parallel shift of the relationship between excitatory input and spiking frequency. Because of the specific cerebellar circuitry, inhibitory inputs may allow Purkinje cells to detect small fluctuations in excitatory input at any mean frequency of input. 6. When climbing fiber input was given in the presence of background asynchronous excitatory and inhibitory inputs the shape of the complex spike in the soma was significantly affected. However, the shape of the spike in the dendrites was almost constant.This difference reflected the more variable excitability of the soma compared with the dendrites. 7. Synchronous activation of basket cell inhibitory synapses during asynchronous activation of granule and stellate cell synapses interrupted somatic spiking. However, the hyperpolarization caused by the basket cell synapse did not penetrate far into the dendrite but stayed localized to the soma and main dendrite. 8. This simulation work demonstrates that a model based on voltage-clamp data and tuned entirely on the response of Purkinje cells to current injection is capable of reproducing a wide range of synaptically activated responses. In the presence of continuous granule cell excitation the model showed a stable in vivo state different from the silent, resting in vitro state. Further, the model suggests that there may be important functional interactions between different types of synaptic inputs. In particular, it makes several specific predictions about the role of stellate cell inhibition.