9ChR2-XXL and GtACR1 are currently the cation and anion ends of the optogenetic single 10 channel current range. These were used in primary rat cortical neurons in vitro to manipulate 11 neuronal firing patterns. ChR2-XXL provides high cation currents via elevated light sensitivity 12and a prolonged open state. Stimulating ChR2-XXL expressing putative presynaptic neurons 13 induced neurotransmission. Moreover, stable depolarisation block could be generated in single 14 neurons using ChR2-XXL, proving that ChR2-XXL is a promising candidate for in vivo 15 applications of optogenetics, for example to treat peripheral neuropathic pain. We also 16 addressed an anion channelrhodopsin (GtACR1) for the next generation of optogenetic neuronal 17 inhibition in primary rat cortical neurons. GtACR1's light-gated chloride conduction was verified 18 in primary neurons and the efficient photoinhibition of action potentials, including spontaneous 19 activity, was shown. Our data also implies that the chloride concentration in neurons decreases 20 during neural development. In both cases, we find surprising applications of these high current 21 channels. For ChR2-XXL inhibition and stimulation are possible, while for GtACR1 the role of Cl -22 during neural development becomes a new optogenetic target. 23