After-hyperpolarization promotes the firing of mitral cells through a voltage dependent modification of action potential threshold

Abstract

In the olfactory bulb, mitral cells (MCs) display a spontaneous firing that is characterized by bursts of action potentials (APs) intermixed with silent periods. Intra-burst firing frequency and duration are heterogeneous among MCs and increase with membrane depolarization. By using patch clamp recording on rat slices, we dissected out the intrinsic properties responsible of this bursting activity. We showed that the threshold of AP generation dynamically changes as a function of the preceding trajectory of the membrane potential. In fact, the AP threshold became more negative when the membrane was hyperpolarized and had a recovering rate inversely proportional to the membrane repolarization rate. Such variations appeared to be produced by changes in the inactivation state of voltage dependent Na⁺ channels. Thus, AP initiation was favored by hyperpolarizing events, such as negative membrane oscillations or inhibitory synaptic input. After the first AP, the following fast afterhyperpolarization (fast AHP) brought the threshold to more negative values and then promoted the emission of the following AP. This phenomenon was repeated for each AP of the burst making the fast AHP a regenerative mechanism that sustained the firing, AHP with larger amplitudes and faster repolarizations being associated with larger and higher frequency bursts. Burst termination was found to be due to the development of a slow repolarization component of the AHP (slow AHP). Overall, the AHP characteristics appeared as a major determinant of the bursting properties.

Significance statement

Mitral cells (MCs) in the olfactory bulb are the main relay of olfactory information towards higher cortical areas and their firing activity provides a substrate for olfactory information. The MC intrinsic dynamics generate a discharge of action potentials (APs) in burst patterns whose underlying mechanisms are not yet elucidated. Here, we show the importance of the AP after-hyperpolarization (AHP) in this process. The fast AHP component increases the availability of sodium channels which facilitates the generation of burst discharge. In addition, the late manifestation of the slow AHP component returns the availability of sodium channel to their initial state and leads to the termination of burst. Overall we demonstrate that burst properties of MCs are determined by AHP characteristics.