Electrophysiological and metabolic interactions between axons and glia in crayfish and squid

Synthesis and release of N-acetylaspartylglutamate (NAAG) by crayfish nerve fibers: implications for axon–glia signaling

“…Glutamate uptake inhibitors used to enhance the accumulation of radiolabel in the bath were ine¡ective in enhancing stimulation-induced radiolabel appearance. Nonetheless, pharmacological investigations from this and other laboratories clearly implicated glutamate receptors and glutamate as the putative agent released to the adaxonal space to initiate electrophysiological and metabolic responses by the associated glia (Lieberman et al, 1994).…”

“…The major premises of this investigation derive from the ¢ndings that: (a) communication between giant invertebrate axons and their associated glia is essential for maintenance of adaxonal space ion homeostasis and preservation of nervous system electrical signaling (Lieberman et al, 1994); (b) communication between axons and glia in non-synaptic regions of the nervous system is mediated by agonists of both N-methyl-Daspartate (NMDA) and non-NMDA glutamate receptors (Villegas, 1978;Lieberman et al, 1989;Evans et al, 1992;Lieberman and Sanzenbacher, 1992;Villegas, 1995;Gafurov et al, 2001); and (c) the axon^glia signaling agent is released during action potential generation in proportion to the product of action potential frequency and stimulation time (Lieberman et al, 1989;Gafurov et al, 2001).…”

“…The same cannulae were used subse-quently to internally perfuse the axon with NCS to disperse and wash out any remaining axoplasm (Lieberman et al, 1990). Internally perfused nerve ¢bers, with their intact sheaths, consist of axon cell membrane and of periaxonal glial cells as the only intact cellular element (Lieberman et al, 1994). They were isolated from the nerve cord and disrupted in distilled water to liberate the cytoplasmic contents of the glial cells, which constituted the glial samples.…”

“…In the ¢rst systematic study of the role of NAAG in axon-to-glia signaling (Gafurov et al, 2001), we have demonstrated that NAAG application to cray¢sh MGNFs hyperpolarized the associated glial cells, comparable to the e¡ect of L-glutamate on squid and cray¢sh glial cells (Evans et al, 1992;Lieberman et al, 1994). The actions of NAAG, glutamate and stimulation were shown to be mediated by Group II metabotropic glutamate receptors.…”

“…Early studies of interactions between stimulated cray¢sh or squid giant axons and their associated Schwann-like glial cells provided strong evidence that L-glutamate released from axons activates metabolic and electrical responses of glia that modulate the ionic microenvironment at non-synaptic regions of the nervous system (Villegas, 1978(Villegas, , 1984(Villegas, , 1995Lieberman et al, 1989Lieberman et al, , 1994Lieberman and Sanzenbacher, 1992;Evans et al, 1992;Grossfeld et al, 1995). A more recent investigation from our laboratories suggests that N-acetylaspartylglutamate (NAAG), rather than glutamate, is the probable mediator of axon^glia signaling, and that its hydrolysis is the indirect source of glutamate in the adaxonal space (Gafurov et al, 2001).…”