Removal of GABA within Adult Modulatory Systems Alters Electrical Coupling and Allows Expression of an Embryonic-Like Network

Abstract

The maturation and operation of neural networks are known to depend on modulatory neurons. However, whether similar mechanisms may control both adult and developmental plasticity remains poorly investigated. To examine this issue, we have used the lobster stomatogastric nervous system (STNS) to investigate the ontogeny and role of GABAergic modulatory neurons projecting to small pattern generating networks. Using immunocytochemistry, we found that modulatory input neurons to the stomatogastric ganglion (STG) express GABA only after metamorphosis, a time that coincides with the developmental switch from a single to multiple pattern generating networks within the STNS. We demonstrate that blocking GABA synthesis with 3-mercapto-propionic acid within the adult modulatory neurons results in the reconfiguration of the distinct STG networks into a single network that generates a unified embryoniclike motor pattern. Using dye-coupling experiments, we also found that gap-junctional coupling is greater in embryos and GABAdeprived adults exhibiting the unified motor pattern compared with control adults. Furthermore, GABA was found to diminish directly the extent and strength of electrical coupling within adult STG networks. Together, these observations suggest the acquisition of a GABAergic phenotype by modulatory neurons after metamorphosis may induce the reconfiguration of the single embryonic network into multiple adult networks by directly decreasing electrical coupling. The findings also suggest that adult neural networks retain the ability to express typical embryonic characteristics, indicating that network ontogeny can be reversed and that changes in electrical coupling during development may allow the segregation of multiple distinct functional networks from a single large embryonic network.

Complicating connectomes: Electrical coupling creates parallel pathways and degenerate circuit mechanisms

“…This is consistent with either a developmental decrease in electrical coupling, or a consequence of the need to inject much more dye into the significantly larger adult neurons for it to travel into other neurons (Rehm, ). Nonetheless, it has been argued that changes in electrical coupling early in development are critical for the maturation of adult motor patterns (Ducret et al, ; Ducret et al, ).…”

Developmental Regulation of Neuromodulator Function in the Stomatogastric Ganglion of the Lobster,Homarus americanus

“…Alternatively, these differences could be due to the immaturity of the neuromodulatory inputs (Fénelon et al, 1999; Kilman et al, 1999; Ducret et al, 2007; Cape et al, 2008), or developmental differences in the responses of STG neurons to neuromodulators. Therefore, we asked if Val 1 -SIFamide, a peptide that can modulate STG neurons in the adult lobster {Christie, 2006 #246}, was found in the same places in the neuromodulatory inputs of adults and embryos.…”

“…Previous work had shown that the isolated embryonic STG responds to dopamine (DA), crustacean cardioactive peptide (CCAP), gamma-aminobutyric acid (GABA), and histamine (HA) (Richards and Marder, 2000; Pulver et al, 2003; Ducret et al, 2007) (Table 1). Although we did not do a detailed comparison with adult preparations, we tested for the presence of receptors for proctolin and allatostatin type A 3 (A-AST-3), modulators that are both present in the late embryonic STG inputs, and 5-HT, which first appears in the STG inputs during mid-late larval stages (Fénelon et al, 1999; Kilman et al, 1999).…”

“…Using results from the present study and previous studies (Richards and Marder, 2000; Pulver et al, 2003; Ducret et al, 2007), we have summarized the maturity of neuromodulator expression in the late embryonic STNS, the neuromodulator receptor presence in the embryonic STG, and, when possible, compared the neuromodulator receptor function in embryonic and adult STG (Table 1). Receptors for many neuromodulators — in fact, receptors for all modulators tested thus far — are present by the end of embryonic development.…”

“…The STG receives input from descending modulatory projection neurons that terminate in the STG neuropil. The complement of neuromodulatory substances in the projection neuron terminals is incomplete until after larval development, perhaps contributing to the immaturity of embryonic STNS output (Fénelon et al, 1999; Kilman et al, 1999; Ducret et al, 2007; Cape et al, 2008). …”