MGluR-Mediated Calcium Waves that Invade the Soma Regulate Firing in Layer V Medial Prefrontal Cortical Pyramidal Neurons

Abstract

Factors that influence the activity of prefrontal cortex (PFC) pyramidal neurons are likely to play an important role in working memory function. One such factor may be the release of Ca2+ from intracellular stores. Here we investigate the hypothesis that metabotropic glutamate receptors (mGluRs)-mediated waves of internally released Ca2+ can regulate the intrinsic excitability and firing patterns of PFC pyramidal neurons. Synaptic or focal pharmacological activation of mGluRs triggered Ca2+ waves in the dendrites and somata of layer V medial PFC pyramidal neurons. These Ca2+ waves often evoked a transient SK-mediated hyperpolarization followed by a prolonged depolarization that respectively decreased and increased neuronal excitability. Generation of the hyperpolarization depended on whether the Ca2+ wave invaded or came near to the soma. The depolarization also depended on the extent of Ca2+ wave propagation. We tested factors that influence the propagation of Ca2+ waves into the soma. Stimulating more synapses, increasing inositol trisphosphate concentration near the soma, and priming with physiological trains of action potentials all enhanced the amplitude and likelihood of evoking somatic Ca2+ waves. These results suggest that mGluR-mediated Ca2+ waves may regulate firing patterns of PFC pyramidal neurons engaged by working memory, particularly under conditions that favor the propagation of Ca2+ waves into the soma.

Competition between Calcium-Activated K+Channels Determines Cholinergic Action on Firing Properties of Basolateral Amygdala Projection Neurons

“…In BLA projection neurons, SK channel activation was only observed with focal stimulation of the soma and proximal dendrites. The necessity for proximal stimulation is also seen in other brain regions (Fiorillo and Williams, 2000;Gulledge and Stuart, 2005;Hagenston et al, 2007) and may reflect a proximal distribution of IP 3 -sensitive calcium stores (Nakamura et al, 2002;Stutzmann et al, 2003;Power and Sah, 2007). Our data show (Figs.…”

“…However, given that IP 3 -evoked calcium release is primarily restricted to spine-sparse regions of the dendrite (Nakamura et al, 2002;Stutzmann et al, 2003;Power and Sah, 2007), it is unlikely that SK channels on spines would be activated by metabotropic receptor stimulation. Similar results are seen in pyramidal neurons within the prefrontal cortex, where SK channel activation by mGluR stimulation requires somatic invasion of the calcium wave (Hagenston et al, 2007). The relative apamin insensitivity of the AHP evoked by brief trains of APs may be caused by the apparent distribution of SK channels in the soma and spines but not on proximal dendrites.…”

“…Calcium release from internal stores has been found to activate SK channels in other neurons Williams, 1998, 2000;Morikawa et al, 2003;Yamada et al, 2004;Gulledge and Stuart, 2005;Hagenston et al, 2007). Consistent with this mechanism, the outward current activated by muscarinic agonists in BLA neurons was suppressed by bath application of the SK channel blocker apamin (100 nM), with no effect on the calcium rise.…”

“…However, muscarinic stimulation also generates inositol 1,4,5-trisphosphate (IP 3 ) that releases calcium from intracellular stores, a process that is amplified by AP-evoked calcium influx Sah, 2005, 2007). Store-released calcium activates SK calcium-activated potassium channels in midbrain dopamine neurons Williams, 1998, 2000;Morikawa et al, 2003) and cortical pyramidal neurons (Yamada et al, 2004;Gulledge and Stuart, 2005;Hagenston et al, 2007), consequently modulating neuronal excitability.…”

Deviant Ryanodine Receptor-Mediated Calcium Release Resets Synaptic Homeostasis in Presymptomatic 3xTg-AD Mice

“…Presynaptically, calcium is fundamental in neurotransmitter release and paired pulse facilitation (PPF) (Bouchard et al, 2003) (but see Carter et al, 2002). Postsynaptically, ER calcium integrates with synaptically evoked responses (Ross et al, 2005;Watanabe et al, 2006), modulates membrane excitability and channel function (Stutzmann et al, 2003;Hagenston et al, 2008), and initiates gene transcription (Mellström and Naranjo, 2001;Watanabe et al, 2006). Long-term synaptic plasticity is also modulated by ER calcium signaling.…”