Pretreatment with β‐adrenergic receptor agonists facilitates induction of LTP and sharp wave ripple complexes in rodent hippocampus

Abstract

Norepinephrine, is involved in the enhancement of learning and memory formation by regulating synaptic mechanisms through its ability to activate pre- and post-synaptic adrenergic receptors. Here we show that β-agonists of norepinephrine facilitate the induction of both associational LTP and sharp wave ripples (SPW-Rs) in acute slices of rat hippocampus in area CA3. Surprisingly, this facilitating effect persists when slices are only pretreated with β-receptor agonists followed by wash out and application of the unspecific β-adrenoreceptor (βAR) antagonist propranolol. During application of βAR agonists repeated stimulation resulted in facilitated induction of SPW-Rs. Since SPW-Rs are thought to be involved in memory replay we studied the effects of βAR-agonists on spontaneous SPW-Rs in murine hippocampus and found that amplitude and incidence of SPW-Rs increased. These effects involve cyclic-AMP and the activation of protein kinase A and suggest a supportive role in memory consolidation. © 2016 Wiley Periodicals, Inc.

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

“…This mechanism was proven in an in vitro study in the rodent [25]. This study implies an improvement in memory consolidation via increased hippocampal sharp wave ripples.…”

“…Mostly, sharp wave ripples arise from the hippocampus' CA3 subregion and originate during sleep or immobility [24]. In vitro experiments in the rat indicated that ß -adrenoreceptor agonism can facilitate sharp wave ripples and LTP [25], supporting the NA's role in modulating sharp wave ripples as well as synaptic plasticity and thereby hippocampal representations to consolidate memory (Figure 1). …”

“…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].…”

Noradrenergic gating of long-lasting synaptic potentiation in the hippocampus: from neurobiology to translational biomedicine

“…If activation of b-ARs was temporally paired with occurrence of SPW-Rs, conditions for generation of b-LTP could be met. NE is released in response to novelty and arousal (Aston-Jones, Rajkowski, Kubiak, & Alexinsky, 1994;Vankov, Herv e-Minvielle, & Sara, 1995), and application of NE suppresses generation of in vitro SPW-Rs via activation of a1-adrenergic receptors (Ul Haq et al, 2016). However, selective activation of b-ARs increases the incidence of SPW-Rs, and this b-AR-dependent SPW-R facilitation is also observed with washout of NE (Ul Haq et al, 2016).…”

“…NE is released in response to novelty and arousal (Aston-Jones, Rajkowski, Kubiak, & Alexinsky, 1994;Vankov, Herv e-Minvielle, & Sara, 1995), and application of NE suppresses generation of in vitro SPW-Rs via activation of a1-adrenergic receptors (Ul Haq et al, 2016). However, selective activation of b-ARs increases the incidence of SPW-Rs, and this b-AR-dependent SPW-R facilitation is also observed with washout of NE (Ul Haq et al, 2016). This NE-mediated sequence of SPW-R suppression followed by enhancement may enable both an immediate, focused, behavioral response and delayed, but increased, opportunities for synaptic plasticity and memory encoding.…”