Figure 1

Synaptic transmission via classical and peptide cotransmitters is target-specific. (A). Schematic of the Lymnaea CNS, depicting in situ locations of the neurons used in this study. Dorsal surface of the ganglia: L/R, left and right; Ce, cerebral; Pe, pedal; Pl, pleural; P, parietal; V, visceral. Adapted from23. (B). Summary diagram of the neurons and synaptic connections that form the respiratory central pattern generator (rCPG) circuit, and the associated motor neurons that drive opening (expiration) and closing (inspiration) of the pneumostome. (C). Summary diagram of the cardioregulatory network, and the motor neurons implicated in modulating the rate and amplitude of auricular and ventricular contractions. (D). Simultaneous intracellular current clamp recordings of endogenous synapses from an isolated intact CNS preparation, performed in control conditions (i; Lymnaea normal saline), or with AChR antagonists (ii; 5 μM MLA, 10 μM TC, 20 μM TEA) to isolate peptidergic transmission. N = 11. Stimulation of VD4 elicits primarily cholinergic inhibition of RPeD1 (iACh in i, antagonized in ii) and primarily peptidergic excitation of VF (eFMRF in i and ii). Lucifer yellow dye injections illustrate the morphology of identified cardiorespiratory neurons and their projections (iii). N ≥ 3 each. Scale bar, 1 mm. (E). Summary data, mean synaptic response of VF is unchanged by addition of AChR antagonists, indicating primarily peptidergic transmission (excitation of VF measured as number of action potentials induced in response to VD4 burst). P = 0.813 (Paired Samples T-test). (F). Summary data, mean synaptic response of RPeD1 is attenuated by AChR antagonists, indicating primarily cholinergic transmission (inhibition of RPeD1 measured as duration of hyperpolarization and firing cessation (s) induced in response to VD4 burst). **P = 0.003 (Wilcoxon Signed Ranks test). Error bars, SEM. (G). Summary diagram illustrating that synaptic transmission at distinct postsynaptic targets is differentially mediated by classical and peptide neurotransmitters.