Glia: Astrocytic Go-Betweens

RESEARCH HIGHLIGHTS

Nature Reviews Neuroscience | Published online 26 May 2016; doi:10.1038/nrn.2016.72

GLIA Astrocytic go-betweens The release of acetylcholine (ACh) in vivo patch-clamp recordings suggesting that the latter may confer from septal neurons that project to revealed that light stimulation of these their effects on these interneurons via Light-induced the hippocampus is thought to have a cells induced the hyperpolarization glutamate-releasing cells. activation of key role in hippocampal learning and and hence inhibition of granule cells. Other studies have provided memory formation, but the mecha- In hippocampal slices, application of evidence that ACh-induced gluta- the septal nism by which ACh exerts its effects methyllycaconitine (MLA), an antag- mate release from glia can mediate cholinergic on hippocampal circuitry has been onist of nicotinic ACh receptors, delayed excitatory neurotrans- neurons unclear. Now, Beck and colleagues blocked this light-induced inhibition mission, so the authors examined show that ACh released by septal pro- of the granule cells, indicating that whether hilar astrocytes act to relay induced rapid, jection neurons activates glutamate- the inhibition is ACh-dependent. the septal neuron signal. Light- temporary releasing astrocytes in the hilus, which It had been proposed previously induced activation of the septal increases in turn activate GABAergic hilar that ACh from septal neurons excites cholinergic neurons induced rapid, in calcium interneurons, resulting in inhibition GABAergic hilar interneurons, temporary increases in calcium of dentate gyrus granule cells in the which in turn inhibit the granule concentration in these astrocytes. concentration hippocampus. cells. In support of this idea, the Moreover, in hippocampal slices, in these To determine the targets of authors found that light stimulation application of an inhibitor of glial astrocytes. ACh transmission, the authors of cholinergic septal neurons metabolism disrupted granule cell first expressed channelrhodopsin 2 induced an increase in activity in inhibition following light-induced (ChR2) in septal cholinergic neurons fast-spiking putative hilar interneu- activation of septal cholinergic neu- in anaesthetized mice. Subsequent rons, as revealed using in vivo silicon rons. Finally, targeted application of probe recordings. Moreover, in a calcium chelator to hilar astrocytes hippocampal slices, similar increases also reduced granule cell inhibition in light-induced hilar interneuronal following light stimulation and led activity preceded the depolarization to a decrease in the light-induced of granule cells and could be reduced excitation of hilar interneurons, in magnitude through the application suggesting that astrocyte activation of MLA. has a key role within this circuit. The authors next examined Together, these findings describe whether septal cholinergic neurons a means by which ACh exerts its role directly activate hilar interneurons. in memory encoding in the hippo In an attempt to isolate ACh-evoked campus and, in doing so, highlight excitatory postsynaptic potentials an important role for astrocytes in in hilar interneurons, the authors this signalling process. blocked ionotropic glutamate recep- Darran Yates

tor responses in these cells. Strikingly, ORIGINAL ARTICLE Pabst, M. et al. Astrocyte however, this blocked responses in intermediaries of septal cholinergic modulation in hilar interneurons to optogenetic acti- the hippocampus. Neuron http://dx.doi. org/10.1016/j.neuron.2016.04.003 (2016) NPG vation of septal cholinergic neurons,