Dopaminergic modulation of axonal potassium channels and action potential waveform in pyramidal neurons of prefrontal cortex

Abstract

Key points• Dopamine and its receptors in prefrontal cortex (PFC) play an important role in regulating synaptic transmission and PFC-mediated cognitive functions.• Considering that presynaptic action potential waveform can modulate postsynaptic responses, we investigated whether axonal K + channels and action potential waveform are subjected to modulation by dopamine.• Patch-clamp recording from the axon of PFC pyramidal neurons showed that the activation of D1 and D2 dopamine receptors decreased and enhanced axonal K + currents, respectively. Further experiments revealed that intracellular cAMP-PKA pathway was involved in this dopaminergic modulation of axonal K + currents.• Recording from axons disconnected from the soma revealed that the dopaminergic modulation still occurred, indicating the presence of functional dopamine receptors along the axon.• We further demonstrate that axonal action potentials were substantially prolonged by D1 receptor activation. Taken together, our results reveal a new mechanism for dopaminergic modulation of neuronal signalling in PFC.Abstract Voltage-gated K + (K V ) channels play critical roles in shaping neuronal signals. K V channels distributed in the perisomatic regions and thick dendrites of cortical pyramidal neurons have been extensively studied. However, the properties and regulation of K V channels distributed in the thin axons remain unknown. In this study, by performing somatic and axonal patch-clamp recordings from layer 5 pyramidal neurons of prefrontal cortical slices, we showed that the rapidly inactivating A-currents mediated the transient K + currents evoked by action potential (AP) waveform command (K AP ) at the soma, whereas the rapidly activating but slowly inactivating K V 1-mediated D-currents dominated the K AP at the axon. In addition, activation of D1-like receptors for dopamine decreased the axonal K + currents, as a result of an increase in the activity of cAMP-PKA pathway. In contrast, activation of D2-like receptors showed an opposite effect on the axonal K + currents. Further experiments demonstrated that functional D1-like receptors were expressed at the main axon trunk and their activation could broaden the waveforms of axonal APs. Together, these results show that axonal K V channels were subjected to dopamine modulation, and this modulation could regulate the waveforms of propagating APs at the axon, suggesting an important role of dopaminergic modulation of axonal K V channels in regulating neuronal signalling.

Dopamine D2 receptors regulate the action potential threshold by modulating T‐type calcium channels in stellate cells of the medial entorhinal cortex

“…In pyramidal neurons of the prefrontal cortex, activation of D1‐like and D2‐like receptors has the opposite effect on axonal K + currents and thus modulates the AP waveform (Yang et al . ). Activation of axonal muscarinic receptors preferentially lowers the AP threshold and enhances intrinsic excitability and synaptic potential–spike coupling in granule cells through T‐type Ca 2+ channels and K v 7 channels (Martinello et al .…”

Analog modulation of spike‐evoked transmission in CA3 circuits is determined by axonal Kv1.1 channels in a time‐dependent manner

“…where m Soma , m Axon , n, p and r are dynamic activation variables, and h Soma , h Axon and k are dynamic inactivation variables. They evolve according to the following differential equations [adapted from Hu et al (2009) for Nav Soma and Nav Axon , Lazarewicz et al (2002) for K DR , Yang et al (2013) for K v 1.1 and Bischofberger et al (2002) for CaP/Q]:…”

Axonal activity in vivo: technical considerations and implications for the exploration of neural circuits in freely moving animals

“…Great strides have been made in the diffusion weighted imaging of axonal processes (Basser and Pierpaoli, 1996 ), the visualization of axonal projections and anatomical connectivity (Chung et al, 2013 ), as well as in vitro studies examining the details of signal propagation in invertebrate (Bucher and Goaillard, 2011 ; Ballo et al, 2012 ) and mammalian axons (Kole et al, 2007 ; Shu et al, 2007 ; Yang et al, 2013 ; Xia et al, 2014 ). These in vitro studies have shown that axons are more than merely reliable conduits for ordered signal propagation and may be directly involved in complex information processing (Debanne, 2004 ; Bucher and Goaillard, 2011 ; Bakkum et al, 2013 ), contribute to high frequency network oscillations (Traub et al, 2003a , b ; Gloveli et al, 2005 ; Dugladze et al, 2012 ) and possess intrinsic breaking mechanisms that can potentially halt seizure propagation (Meeks et al, 2005 ).…”