Abstract
A-type K+ channels restrain the spread of incoming signals in tufted and apical dendrites of pyramidal neurons resulting in strong compartmentalization. However, the exact subunit composition and functional significance of K+ channels expressed in small diameter proximal dendrites remain poorly understood. We focus on A-type K+ channels expressed in basal and oblique dendrites of cortical layer 3 pyramidal neurons, in ex vivo brain slices from young adult mice. Blocking putative Kv4 subunits with phrixotoxin-2 enhances depolarizing potentials elicited by uncaging RuBi-glutamate at single dendritic spines. A concentration of 4-aminopyridine reported to block Kv1 has no effect on such responses. 4-aminopyridine and phrixotoxin-2 increase supralinear summation of glutamatergic potentials evoked by synchronous activation of clustered spines. The effect of 4-aminopyridine on glutamate responses is simulated in a computational model where the dendritic A-type conductance is distributed homogeneously or in a linear density gradient. Thus, putative Kv4-containing channels depress excitatory inputs at single synapses. The additional recruitment of Kv1 subunits might require the synchronous activation of multiple inputs to regulate the gain of signal integration.
Highlights
Dendritic integration of synaptic potentials is regulated by several biophysical and molecular factors linked to synaptic transmission and changes in intrinsic excitability (Araya, 2014; Branco and Hausser, 2010; Major et al, 2013; Spruston, 2008; Stuart and Spruston, 2015; Williams and Stuart, 2002)
We recorded from the soma of layer 3 (L3) pyramidal neurons in current-clamp mode at 32 °C with pipettes containing Alexa Fluor 594 (150 μM), and imaged portions of basal and apical oblique dendrites using two-photon laser scanning microscopy
Our pharmacological analysis indicated that putative Kv4 channels depress glutamatergic signals elicited at single spines in basal and apical oblique dendrites of L3 pyramidal neurons
Summary
Dendritic integration of synaptic potentials is regulated by several biophysical and molecular factors linked to synaptic transmission and changes in intrinsic excitability (Araya, 2014; Branco and Hausser, 2010; Major et al, 2013; Spruston, 2008; Stuart and Spruston, 2015; Williams and Stuart, 2002). Dendritic patch-clamp recordings from CA1 pyramidal neurons have revealed a functional six-fold increase in IA current density along the proximal to distal path of the main apical dendrite (Hoffman et al, 1997). This distribution in positive gradient restrains dendritic plateau potentials and reduces the amplitude of back-propagating axo-somatic action potentials (Andrasfalvy et al, 2008; Cai et al, 2004) enabling synaptic plasticity and branch-specific storage (Chen et al, 2006, 2011; Frick et al, 2003; Golding et al, 1999; Losonczy and Magee, 2006; Losonczy et al, 2008). In these neurons the interplay between A-type K+ channels and NMDA receptors results in a highly dynamic modulation of the gain of dendritic integration of glutamatergic signals
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