Astroglia is now accepted as an active player in information processing in the central nervous system, playing a role in a variety of vital functions. Astrocytes may influence activity of adjacent neurons via a number of mechanisms, including release of signalling molecules, such as ATP, D-serine and glutamate. In addition, according to the ‘astrocyte-to-neuron lactate shuttle’ hypothesis, astrocytes generate L-Lactate (LL) from glucose or glycogen and deliver it to the extracellular space from where it may be taken up by neurones and consumed as preferred energy substrate (Suzuki et al., 2011). We used optogenetics to stimulate astrocytes in rat organotypic cultured slices containing the locus coeruleus (LC), the largest group of brain noradrenergic (NAergic) neurones. Optogenetic actuators ChR2(H134R) or the rhodopsin-β2-adrenoceptor chimaera Opto-β2-AR (Airan et al., 2009) were introduced with adenoviral vectors and expressed by a transcriptionally enhanced, compact glial fibrillary acidic protein promoter (Liu et al., 2008) to ensure astrocyte-selective expression. We then measured electrophysiological responses in adjacent noradrenergic neurones by patch clamp, or monitored noradrenaline (NA) release using fast-scan cyclic voltammetry. We found that that optogenetic activation of astrocytes leads to excitation of LC neurones. Depolarisations were suppressed by treatment with the glycogen metabolism blocker 1,4-dideoxy-1,4-imino-D-arabinitol (DAB; 500μM) or co-application of D-lactate (2 mM), but not by treatment with the monocarboxylate transporter blocker 4-CIN (100uM). This suggests that the excitation may be triggered by LL, released by activated astrocytes, and acting on a substrate located on the extracellular side of the cell membrane of LC neurones. Exogenously applied LL (0.2 – 20 mM) was also excitatory to LC neurones. These effects were not due to pH or caloric effects of LL as intracellular LL (2 mM), or extracellular pyruvate were ineffective. Using fast scan cyclic voltammetry, we found powerful NA release in response to optogenetic activation of astrocytes or application of LL. These responses were also sensitive to DAB and D-lactate. Microinjection of LL into the LC of urethane (i.p.) anaesthetised rats in vivo caused an increase in arterial blood pressure and changes in EEG qualitatively similar to those of L-glutamate, an established excitatory transmitter. Together, these effects of LL may not be explained by its value as an energy substrate for LC neurons but are consistent with its role as an inter-cellular signalling molecule operating between astrocytes and NAergic neurones. Moreover, they imply an existence of as yet unknown receptor for this new “glio-transmitter”.