Figure 5

Schematic of the feedforward loops proposed to underlie GHRH rhythm generation by SST.

(A) The feedforward loop (FFL) allows precise temporal control over GHRH neuron electrical activity via dynamic effects on inhibitory and stimulatory drive. Strengths of GIRK activation, glutamatergic and GABAergic inputs are colored in red, green and violet, respectively. Grey shaded areas illustrate episodes of GHRH neuron firing. (B) At the circuit level, the FFL motifs consist of a primary regulator, SST, which inhibits secondary regulators (glutamatergic or GABAergic inputs) that synapse with GHRH neurons. The network motif involving glutamatergic inputs provides a delayed excitatory source (coherent FFL; see¹² for definitions), whereas the motif with GABAergic inputs acts as a pulser (incoherent FFL). Both sst1 and sst2 receptors are involved in SST responses, with sst1 receptors notably acting to intermittently delay GABA current onset (pulse generator). The sexually dimorphic spiking rhythms recorded in GHRH neurons were associated with a sex-dependent SST-regulation of linked FFLs but not GIRK currents in GHRH neurons (signs colored in red). Signs for inhibitory and stimulatory interneuron effects are colored in violet and green, respectively. Sign thickness represents the response magnitude. The “AND” gate sign represents the link between both coherent and incoherent FFLs, which recurs within the arcuate nucleus.