| Popis: |
Most neuronal circuits receive at least two functionally distinct input types (intrinsic vs. extrinsic; sensory vs. motor; etc). In many pyramidal neuron based microcircuits integration of these two input signals can proceed nonlinearly through the production of active dendritic voltage signals. For example, appropriately timed, perisomatically located, hippocampal (SC) and distal dendrite targeting entorhinal (EC3) input produces a distal dendritic Ca2+ plateau potential that drives burst firing output from CA1 pyramidal neurons in vitro. Related signals have been observed in neocortical pyramidal neurons. Until recently it was unknown whether these events occurred in vivo and, if so, during what behavioral states. Here we used simultaneous whole-cell patch and field potential recordings in head-fixed mice running on a linear track treadmill to study this dendritic plateau driven burst firing (plateaus) in CA1 neurons. We find that during locomotion dendritic plateau potentials occur within the neuron’s place field with initiation probability peaking near the peak of the firing field. Plateaus produce a large (32±4mV; n=12), slow (duration; 51±7ms) somatic depolarization that appears similar to that measured in vitro. Interestingly, plateaus exhibit a dramatic level of theta-phase modulation (~97%) that peaks late in the theta cycle (~330°). This late phase peak in plateau potential initiation is near the theta-phase preference of EC3 inputs, suggesting a theta-phase dependent interaction of SC and EC3 inputs. We tested this idea by manipulating the phase of SC inputs by injecting phase adjusted theta frequency currents into CA1 somas. Biasing AP firing earlier in the theta phase decreased plateau probability to ~48% of control whereas biasing AP firing later in phase increased plateau probability 276%. We next directly examined the role of EC3 inputs by inactivating the EC3 axons in CA1 via local light activation of axons expressing archaerhodopsin. This manipulation reduced the probability of plateau initiation by ~40% and decreased the duration of the plateaus ~60%. These data indicate that CA1 pyramidal cells compare theta-phase relations of SC and EC3 inputs with backpropagating action potentials acting as a link between the two isolated subcellular input integration compartments. |
