The bag cells of Aplysia as a multitransmitter system: identification of alpha bag cell peptide as a second neurotransmitter

Abstract

The bag cell neurons of the marine mollusk, Aplysia, are a putative multitransmitter system that utilizes two or more peptide transmitters derived from a common precursor protein. Two putative transmitters are egg-laying hormone (ELH), a 36 amino acid peptide that induces egg laying and mediates bag cell-induced excitatory effects on certain abdominal ganglion neurons, and alpha-bag cell peptide (alpha BCP), which mimics bag cell-induced inhibition of the left upper quadrant (LUQ) neurons and the depolarization of the bag cells that occurs during the bag cell burst discharge. Alpha BCP was previously purified from bag cell extracts in three neuroactive forms: alpha BCP(1-9), a nine amino acid peptide encoded on the ELH/BCP precursor protein, and two NH2-terminal fragments, alpha BCP(1-8) and alpha BCP(1-7). Analyzing bag cell-induced inhibition of LUQ neurons, we report here that alpha BCP fulfills the main criteria for transmitter identification: stimulation of individual bag cells produces inhibition of the neurons; inhibitory activity is present in releasate collected following an elicited bag cell burst discharge in the presence of protease inhibitors; alpha BCP(1-9) and alpha BCP(1-8) are detected in the releasate in the presence of protease inhibitors; alpha BCP is rapidly inactivated after release, as indicated by the lack of detectable alpha BCP or inhibitory activity in the releasate in the absence of protease inhibitors, and by the increase in potency of the arterially perfused peptide in the presence of protease inhibitors; alpha BCP and the endogenously released transmitter produce apparently identical changes in membrane conductance; bag cell-induced inhibition is reduced or abolished following desensitization of the inhibitory response by long-term application of high concentrations of alpha BCP. The results provide additional evidence that the bag cells are a multitransmitter system and also suggest that many of the physiological properties of alpha BCP-mediated neurotransmission differ from those of ELH. First, unlike ELH, alpha BCP is rapidly inactivated after release. Second, alpha BCP(1-9) may be activated by carboxypeptidase cleavage since alpha BCP(1-8) and alpha BCP(1-7) are 30 and 10X as potent, respectively, as alpha BCP(1-9). Third, the inhibitory action of alpha BCP on its targets has a more rapid onset and a shorter time course than the excitatory actions of ELH. Thus, alpha BCP may diffuse to less distant targets than ELH and serve to regulate the more rapidly occurring neural events underlying egg-laying behavior.

A newly identified extrinsic input triggers a distinct gastric mill rhythmviaactivation of modulatory projection neurons

“…Given the sensitivity of MCN1 and CPN2 to relatively brief POC stimulation, there may well be times when this input acts largely or exclusively as a local modulator of neuronal activity, whereas at other times its activation results in both paracrine and endocrine actions. Previous studies in other systems have established the ability of the same neurons to release signaling molecules that act both locally, in a paracrine fashion, and as circulating hormones (Mayeri, 1979;Sigvardt et al, 1986;Jung and Scheller, 1991;Loechner and Kaczmarek, 1994;Ludwig and Pittman, 2003;Fort et al, 2004;Oliet et al, 2007).…”

Different Proctolin Neurons Elicit Distinct Motor Patterns from a Multifunctional Neuronal Network

“…It is also possible that a shared neuromodulator will affect a network in different ways when released by distinct modulatory neurons, even in the absence of different cotransmitters. For neuropeptide transmitters, this could result from a compartmentalization of their actions, as would occur if their range of influence was limited by extracellular peptidases (Sigvardt et al, 1986;Saleh et al, 1996) or if they were released either at different distances from their receptors or in different amounts (Vilim et al, 1996).…”

Neurotransmission: peptide transmitters turn 36

“…However, prior to Jan and Jan's 1982 paper, these concepts were not yet fully established at the level of identified neurons and synapses. The fact that cotransmission, in particular, was already evident nearly four decades ago likely is surprising to some because, despite a smattering of subsequent studies (Adams and O'Shea, 1983;Sigvardt et al, 1986;Bishop et al, 1987;Whim and Lloyd, 1989;Kupfermann, 1991;Nusbaum et al, 2001), it has only been during the past 10 years or so that the functional consequences of co-transmission have become a growth industry (Vaaga et al, 2014;Nusbaum et al, 2017).…”