Dendritic A-current in Rhythmically Active PreBötzinger Complex Neurons in Organotypic Cultures from Newborn Mice.

The brainstem preBotzinger complex (preBotC) generates the inspiratory rhythm for breathing. The onset of neural activity that precipitates the inspiratory phase of the respiratory cycle may depend on the activity of type-1 preBotC neurons, which exhibit a transient outward K+ current, I-A Inspiratory rhythm generation can be studied ex vivo because the preBotC remains rhythmically active in vitro, both in acute brainstem slices and organotypic cultures. Advantageous optical conditions in organotypic slice cultures from newborn mice of either sex allowed us to investigate how I-A impacts Ca2+ transients occurring in the dendrites of rhythmically active type-1 preBotC neurons. The amplitude of dendritic Ca2+ transients evoked via voltage increases originating from the soma significantly increased after an I-A antagonist, 4-aminopyridine (4-AP), was applied to the perfusion bath or to local dendritic regions. Similarly, glutamate-evoked postsynaptic depolarizations recorded at the soma increased in amplitude when 4-AP was coapplied with glutamate at distal dendritic locations. We conclude that I-A is expressed on type-1 preBotC neuron dendrites. We propose that I-A filters synaptic input, shunting sparse excitation, while enabling temporally summated events to pass more readily as a result of I-A inactivation. Dendritic I-A in rhythmically active preBotC neurons could thus ensure that inspiratory motor activity does not occur until excitatory synaptic drive is synchronized and well coordinated among cellular constituents of the preBotC during inspiratory rhythmogenesis. The biophysical properties of dendritic I-A might thus promote robustness and regularity of breathing rhythms.