Non-technical summary The hippocampus is a neural structure that is critical for some forms of memory function. It performs this function through the ability of its neurons to fire patterns of activity that encode information and the ability of the synaptic connections between neurons to strengthen or weaken. Glutamate, an important synaptic neurotransmitter, can activate different types of receptors, including metabotropic glutamate receptors (mGluRs). mGluRs have been shown to be important for learning and memory. It has also been shown that changes in mGluR type 5 might contribute to mental retardation and autism, suggesting that manipulation of mGluR5 might reduce their symptoms. In this study we examined how mGluR activation can activate neuron membrane channels (SK and TRPC) in hippocampal neurons that regulate their activity. Our findings suggest that mGluR activation of SK and TRPC channels are likely to be important for sculpting patterns of activity that encode information by the hippocampus.Abstract Group I metabotropic glutamate receptors (mGluRs) play an essential role in cognitive function. Their activation results in a wide array of cellular and molecular responses that are mediated by multiple signalling cascades. In this study, we focused on Group I mGluR activation of IP 3 R-mediated intracellular Ca 2+ waves and their role in activating Ca 2+ -dependent ion channels in CA1 pyramidal neurons. Using whole-cell patch-clamp recordings and high-speed Ca 2+ fluorescence imaging in acute hippocampal brain slices, we show that synaptic and pharmacological stimulation of mGluRs triggers intracellular Ca 2+ waves and a biphasic electrical response composed of a transient Ca 2+ -dependent SK channel-mediated hyperpolarization and a TRPC-mediated sustained depolarization. The generation and magnitude of the SK channel-mediated hyperpolarization depended solely on the rise in intracellular Ca 2+ concentration ([Ca 2+ ] i ), whereas the TRPC channel-mediated depolarization required both a small rise in [Ca 2+ ] i and mGluR activation. Furthermore, the TRPC-mediated current was suppressed by forskolin-induced rises in cAMP. We also show that SK-and TRPC-mediated currents robustly modulate pyramidal neuron excitability by decreasing and increasing their firing frequency, respectively. These findings provide additional evidence that mGluR-mediated synaptic transmission makes an important contribution to regulating the output of hippocampal neurons through intracellular Ca 2+ wave activation of SK and TRPC channels. cAMP provides an additional level of regulation by modulating TRPC-mediated sustained depolarization that we propose to be important for stabilizing periods of sustained firing.