Selective tuning of hippocampal oscillations by phasic locus coeruleus activation in awake male rats

Abstract

Theta and gamma oscillations are thought to provide signal sets that promote neural coding of cognitive processes. Over 40 yrs ago, Jeffrey Gray reported event-related changes in a narrow band of hippocampal theta (7.5-8.5 Hz) which appeared to involve norepinephrine (NE) release from, the noradrenergic nucleus, the locus coeruleus (LC). These event-related alterations in EEG were elicited by novelty, attentional changes, the use of preparatory signals, and signal-mismatch events. Gray et al. have since provided indirect evidence that supports the role of NE in the modulation of 7.5- to 8.5-Hz oscillations in the hippocampus, but studies investigating the effects of direct LC activation in awake rats have been lacking. In the present study, dentate gyrus EEG was examined during glutamatergic activation of the LC in awake male rats in relation to plasticity effects on simultaneously recorded perforant path-evoked field potentials. Glutamate-injected animals were divided into three groups based on histological and plasticity outcomes; perforant path stimulated controls were also included. The three injected groups were: (1) rats with positive LC placements, demonstrating NE-LTP of the dentate gyrus evoked potential, (2) rats with positive LC placements, without NE-LTP, and (3) Non-LC injected controls. Activation of the LC in awake rats demonstrating NE-LTP increased the relative power of 7- to 9-Hz theta, a result masked in broader 4- to 12-Hz analysis. Comparatively, urethane-anesthetized rats showed an increase in 5-7 Hz, but not 7- to 9-Hz theta with LC activation. Discriminative analysis in the approximate theta band predicted by Gray (7.4-8.5 Hz) revealed that awake rats demonstrating NE-LTP had increased relative power in this narrow frequency compared to rats receiving perforant path only (noninjected) and Non-LC injected rats. Transiently reduced gamma (20-40 Hz) relative power was most commonly observed in rats with verified LC placements failing to express NE-LTP. Given current theories of LC function, these results suggest oscillatory tuning within the theta and gamma range may facilitate shifts in cognitive set.

Locus Coeruleus in time with the making of memories

“…16 2014]. This has already been suggested by C. Harley who found that activation of LC neurons by local glutamate infusion 'selectively tunes' hippocampal theta oscillations and reduces the frequency of the gamma oscillation [46,47]. Such actions of NE on oscillatory rhythms in cortex and hippocampus could well be the mechanism by which the LC-NE system 'resets' network activity.…”

The Longevity of Hippocampus-Dependent Memory Is Orchestrated by the Locus Coeruleus-Noradrenergic System

“…We know for one that LC activation is followed by an increase in theta power parallel to the LTP in rodents [72]. On the other hand, no LTP was observed when gamma frequencies are ameliorated after LC activation [72].…”

“…We know for one that LC activation is followed by an increase in theta power parallel to the LTP in rodents [72]. On the other hand, no LTP was observed when gamma frequencies are ameliorated after LC activation [72]. LC-facilitated CA1 LTD in rats is accompanied by the transient suppression of theta frequencies [27], which suggests that a theta frequency increase or suppression after LC activation might be responsible for directing synaptic plasticity (LTP or LTD) and forming subsequent memories.…”

“…However, the exact molecular mechanism by which NA sets the threshold of synaptic long-term plasticity remains unclear. On the network level, potential mechanism candidates for the threshold shifting of LTP or LTD are an NA-facilitated increase or suppression in theta frequencies [27, 72]. It is conceivable that the set point modulation is also induced by DA released from LC terminals.…”

“…The LC projects also to the CA1 and CA3 region of the hippocampus [82]. The main mechanisms involved in how memory is primed by NA and DA are indicated in boxes at specific hippocampal subregions [25–28, 33, 63, 72]. Moreover, two other brain structures such as the basolateral amygdala (BLA) and the prefrontal cortex (PFC) receive projections from the LC [3, 4] and participate in noradrenergic and dopaminergic modulation of hippocampus-based memory [6, 49, 61].…”