Back-propagation of action potentials from GnRH somata to dendrites. Current pulses applied to somata induced action potentials. These action potentials were subsequently detected at dendrite recording sites that were at least 250 μm from somata.

Differences in action potential thresholds for simulated synapses applied along the length of model GnRH dendrites. A, The minimum synaptic strength to initiate a spike varies with the location on the dendrite. Each curve indicates a dendrite branch, either the single dendrite in the bipolar cell model or each of the two branches of model with a branching dendrite. Simulated synapses were placed on dendrites at increasing distances from the soma. Action potential thresholds reach a maximum of 1.8 nS at 118 μm of dendrite length in the bipolar cell and 2.9 nS at 150 μm of dendrite length in the branching cell and then decreased to 0.41 and 0.23 nS, respectively, at the distal tips of the dendrites. B, Shift from somatic to dendritic spike initiation along the length of the model GnRH dendrite. In each panel, the black trace corresponds to somatic membrane potential changes (black electrode). The colored traces indicate voltages in dendrite compartments whose recording electrode and simulated voltage trace has the corresponding color. Voltage responses in the top panels correspond to activation of a simulated synapse at 127 μm of dendrite length (indicated by the red triangle with a single asterisk). Voltage responses in the lower panels correspond to activation of a simulated synapse at 499 μm of dendrite length (indicated by the red triangle with a double asterisk). In i, the postsynaptic potential is seen first in the dendrite (blue), but the action potential is initiated at the soma (black). The purple and red traces show active back-propagation of the somatic action potential into dendrite compartments at 298 μm of dendrite length (ii; purple trace) and 499 μm of dendrite length (iii; red trace). In the upper traces, the black somatic spike precedes spikes in all dendrite compartments, and thus, these action potentials have somatic sites of initiation. In the lower panels, activation of the simulated synapse at 499 μm of dendrite length led to a locally initiated action potential in the dendrite (vi) where the dendrite action potential (red trace) precedes the somatic action potential (black trace). The action potential was actively propagated from its initiation site in the distal dendrite (at 499 μm) toward the soma to more proximal dendrite compartments at 298 μm (purple trace in v) and 102 μm (blue trace in iv) and then invades the soma (black trace in iv–vi). Accordingly, regions on either side of the maximal threshold in A differ in spike initiation zone. The axonal compartments have been removed from the model neuron in the figure but were included during simulations.

GnRH neuron dendrites express Na⁺_v channels. A, Projected confocal image of Na⁺_v-ir in the CA1 hippocampus of GnRH-GFP mice; B, single optical slice (0.36 μm) through two neurons (asterisks) showing with membrane-localized Na⁺_v-ir; C, omitting Na⁺_v primary antibody eliminates Na⁺_v-ir; D, projected confocal stack of a GnRH soma and proximal dendrite (green) and Na⁺_v-ir (red): i–iii, below, single optical slices (0.36 μm) corresponding to regions indicated by white boxes in D; E, low-power projected confocal image of GnRH neuron cell bodies and dendrites and Na⁺_v-ir; F, projected confocal stack of a portion of dendrite 390 μm from the cell body of a GnRH neuron shown in E (white box); i–iii, far right, single optical slices (0.36 μm) corresponding to regions indicated by white boxes in F, with arrows highlighting yellow pixels indicative of Na⁺_v-ir localized in the distal segment of a GnRH dendrite; G, omitting Na⁺_v primary antibody eliminates Na⁺_v-ir. Scale bars, 10 μm (A–E) and 5 μm (G).

Dendrites exhibit spontaneous action potential initiation in GnRH neurons. Simultaneous recordings from GnRH somata (thin traces) and dendrites (thick traces) in two neurons reveal action potentials originating in dendrites in one neuron (action potentials A and B), whereas others originate in somata of a different GnRH neuron (action potentials C and D). In a third GnRH neuron, action potentials have dendritic sites of origin (action potentials E and F).