FIGURE 2.

Neurotransmitter phenotype of the MFs during development and its plasticity in the adult. (A) During the first 5 days of life, MFs are GABAergic. Minimal stimulation provokes synaptic currents that are partially inhibited by the glutamatergic antagonist DNQX and completely blocked by the GABAA-R antagonist, picrotoxin (modified from Safiulina et al., 2006). (B) From postnatal day 5–6 and up to the end of postnatal day 21–22, the synaptic responses evoked by stimulation of MF boutons can consist of inward and outward currents, consistent with co-release of glutamate and GABA (red traces at Vh = 30 mV), whereby their reversal potential is much more positive than that expected for a GABA-R-mediated current or much more negative than that expected for a glutamate-R-mediated current. Block of glutamatergic receptors isolates GABAergic responses, shifting the reversal potential to a more negative value (modified from Beltrán and Gutiérrez, 2012). (C) Other responses observed by stimulation of single, identified MF boutons during this period consist of glutamatergic-only or GABAergic-only currents (modified from Beltrán and Gutiérrez, 2012). (D) Stimulation of MFs in adult preparations provoke glutamate-R-mediated responses, however, seizures or repeated LTP-like stimulation up-regulate the GABAergic markers and MF activation provokes monosynaptic GABAR-mediated responses in their target cells. The release of glutamate and GABA from the MFs can serve presynaptic modulation of parallel MFs or of the releasing fibers themselves. Mossy fibers as well as the post-synaptic sites contain glutamate and GABA receptors. Moreover, the MFs themselves express these and receptors to BDNF, endocannabinoids, kainite, and metabotropic glutamate and GABAreceptors, which have been shown to modulate both glutamate and GABA release.