Proximal Persistent Na⁺Channels Drive Spike Afterdepolarizations and Associated Bursting in Adult CA1 Pyramidal Cells

Abstract

In many principal brain neurons, the fast, all-or-none Na ϩ spike initiated at the proximal axon is followed by a slow, graded afterdepolarization (ADP). The spike ADP is critically important in determining the firing mode of many neurons; large ADPs cause neurons to fire bursts of spikes rather than solitary spikes. Nonetheless, not much is known about how and where spike ADPs are initiated. We addressed these questions in adult CA1 pyramidal cells, which manifest conspicuous somatic spike ADPs and an associated propensity for bursting, using sharp and patch microelectrode recordings in acutely isolated hippocampal slices and single neurons. Voltage-clamp commands mimicking spike waveforms evoked transient Na ϩ spike currents that declined quickly after the spike but were followed by substantial sustained Na ϩ spike aftercurrents. Drugs that blocked the persistent Na ϩ current (I NaP ), markedly suppressed the sustained Na ϩ spike aftercurrents, as well as spike ADPs and associated bursting. Ca 2ϩ spike aftercurrents were much smaller, and reducing them had no noticeable effect on the spike ADPs. Truncating the apical dendrites affected neither spike ADPs nor the firing modes of these neurons. Application of I NaP blockers to truncated neurons, or their focal application to the somatic region of intact neurons, suppressed spike ADPs and associated bursting, whereas their focal application to distal dendrites did not. We conclude that the somatic spike ADPs are generated predominantly by persistent Na ϩ channels located at or near the soma. Through this action, proximal I NaP critically determines the firing mode and spike output of adult CA1 pyramidal cells.

Study on dynamic characteristics’ change of hippocampal neuron reduced models caused by the Alzheimer’s disease

“…They have studied electrophysiological characteristics of the neuron under the morbid state of AD, and have acquired many research findings and conclusions [15,18,20,22]. Xiaoliang Wang [15] simulated the morbid state of AD by injecting the aggregated Aβ [25][26][27][28][29][30][31][32][33][34][35] into the lateral ventricle. They recorded and studied the electrophysiological characteristics' change of the hippocampal pyramid neuron's voltage-gated currents (the A-type instantaneous K + current (I A ) and the delay rectification K + current (I Kdr )) under the morbid state of AD.…”

“…(1) The aggregated Aβ [25][26][27][28][29][30][31][32][33][34][35] 's injecting into the lateral ventricle in one shot has some effect on the amplitude and the density of A-type instantaneous K + current (I A ). But from the neurodynamics angle, A-type instantaneous K + current's stable activation dynamic characteristics and stable inactivation dynamic characteristics have no significant difference [15].…”

“…But from the neurodynamics angle, A-type instantaneous K + current's stable activation dynamic characteristics and stable inactivation dynamic characteristics have no significant difference [15]. (2) The aggregated Aβ [25][26][27][28][29][30][31][32][33][34][35] 's injecting into the lateral ventricle in one shot has great effect on the amplitude and the density of the delay rectification K + current (I Kdr ).…”

“…The existing findings have proved that AD can cause electrophysiological characteristics' change of the hippocampal neuron, and especially can cause change of the potassium ion channel characteristics [1,18,21]. Dependent on electrophysiological experiments and new technologies, such as optics imaging, some models of hippocampal pyramidal neurons based on ionic conductance have been successfully constructed [3,4,5,6,9,[11][12][13][14]19,[23][24][25][26][27].…”

“…Yue et al found that bursting behavior persists in adult CA1 pyramidal cells after almost complete truncation of the apical dendrites. The bursting mechanism is different from the 'ping-pong' mechanism, which depends on integrity of apical dendrites [25][26][27]. Based on the CA1 pyramidal neuron's membrane ionic channel theory and its electrophysiological experimental data, according to the basic frames of the Hodgkin-Huxley(H-H) class of neuron models, Golomb et al developed the one-compartment model of CA1 pyramidal neuron [5], which is different from the former multi-compartment cable model of the hippocampal pyramid neuron.…”