Locus Ceruleus Activation Suppresses Feedforward Interneurons and Reduces β-γ Electroencephalogram Frequencies While It Enhances θ Frequencies in Rat Dentate Gyrus

Abstract

The locus ceruleus is activated by novel stimuli, and its activation promotes learning and memory. Phasic activation of locus ceruleus neurons by glutamate enhances the dentate gyrus population spike amplitude and results in long-term potentiation of synaptic responses recorded after 24 h. Cholinergic activation of locus ceruleus neurons increases hippocampal . At the level of the cellular network, it is not clear how the potentiating effects of norepinephrine are mediated. Previous studies show that exogenous norepinephrine enhances inhibitory interneuron firing in the dentate gyrus. This finding appears at odds with evidence for potentiation. In this study, natural release of norepinephrine was induced by glutamate activation of locus ceruleus while we recorded EEGs and physiologically identified interneurons in the dentate gyrus of urethane-anesthetized rats. Feedforward neurons were inhibited (ϳ1-2 min) by locus ceruleus activation. Feedback interneurons showed both increased and decreased activity, whereas granule cells increased firing as predicted by evoked potential studies. EEG results replicated an increase in power (4 -8 Hz) with locus ceruleus activation, but the effect with glutamatergic locus ceruleus activation was transient (ϳ1-2 min). ␤-␥ Frequencies were also transiently suppressed. Together, the data suggest that locus ceruleus activation enhances the throughput of concomitant sensory input by reducing feedforward inhibitory interneuron activity, which may reduce "binding" in existing cell assemblies, and enhances the conditions for synaptic plasticity through disinhibition, promotion of 4 -8 Hz , and noradrenergic potentiation to facilitate the building of new representations.

Noradrenergic Signaling in Infralimbic Cortex Increases Cell Excitability and Strengthens Memory for Fear Extinction

“…In the hippocampus, activation of ␤-receptors has been shown to increase calcium current (Huang et al, 1998a,b) and kinase activity (Winder et al, 1999). This noradrenergic amplification of intracellular processes results in increased responsiveness of cells to synaptic inputs (Brown et al, 2005). For example, ␤-receptor activation alone is not sufficient to induce hippocampal long-term potentiation (LTP), but enables LTP in response to subthreshold stimuli (Thomas et al, 1996;Katsuki et al, 1997;Gelinas and Nguyen, 2005).…”

Hypocretin (orexin) is critical in sustaining theta/gamma-rich waking behaviors that drive sleep need

“…Hcrt signaling appears thus critical to limiting slow-γ activity in baseline dark-phase TDW, whereas under SD other arousal pathways sustain a TDW state largely lacking this activity. Supporting this, locus coeruleus norepinephrine (NE) cell stimulation, as likely occurs in SD, suppresses β (12-to 20-Hz) and slow-γ (20-to 40-Hz) activity in rats (50).…”

Learning, the P3, and the Locus Coeruleus-Norepinephrine System

“…Finally, there is evidence that NE suppresses intracortical and feedback synaptic transmission, while sparing, or even boosting, thalamocortical processing (e.g., Kobayashi, 2000). For example, NE can change the mode of activity of thalamic neurons from burst to spike mode, necessary for the accurate transfer of incoming information to the neocortex (McCormick, 1992); and LC activation enhances the processing of concomitant sensory input by reducing feedforward inhibitory interneuron activity, and reduces"binding" oscillations hypothesized to stabilize existing memories (Brown, Walling, Milway, & Harley, 2005). These actions promote learning by favoring bottom-up, sensory signals at the expense of top-down, expectationdriven signals (cf.…”