Noradrenergic Suppression of Synaptic Transmission May Influence Cortical Signal-to-Noise Ratio

Abstract

Norepinephrine has been proposed to influence signal-to-noise ratio within cortical structures, but the exact cellular mechanisms underlying this influence have not been described in detail. Here we present data on a cellular effect of norepinephrine that could contribute to the influence on signal-to-noise ratio. In brain slice preparations of the rat piriform (olfactory) cortex, perfusion of norepinephrine causes a dose-dependent suppression of excitatory synaptic potentials in the layer containing synapses among pyramidal cells in the cortex (layer Ib), while having a weaker effect on synaptic potentials in the afferent fiber layer (layer Ia). Effects of norepinephrine were similar in dose-response characteristics and laminar selectivity to the effects of the cholinergic agonist carbachol, and combined perfusion of both agonists caused effects similar to an equivalent concentration of a single agonist. In a computational model of the piriform cortex, we have analyzed the effect of noradrenergic suppression of synaptic transmission on signal-to-noise ratio. The selective suppression of excitatory intrinsic connectivity decreases the background activity of modeled neurons relative to the activity of neurons receiving direct afferent input. This can be interpreted as an increase in signal-to-noise ratio, but the term noise does not accurately characterize activity dependent on the intrinsic spread of excitation, which would more accurately be described as interpretation or retrieval. Increases in levels of norepinephrine mediated by locus coeruleus activity appear to enhance the influence of extrinsic input on cortical representations, allowing a pulse of norepinephrine in an arousing context to mediate formation of memories with a strong influence of environmental variables.

Free recall and recognition in a network model of the hippocampus: simulating effects of scopolamine on human memory function

“…We feel these effects can be accounted for on the basis of the same set cellular effects of scopolamine within neocortical structures. For example, detection of a specific stimulus requires a strong influence of afferent input to the cortex, but the decreased depolarization and stronger intrinsic excitation present with scopolamine would decrease the afferent drive relative to intrinsic activity-thereby impairing the influence of external stimuli on cortical activity [49,121,122]. In the extreme case, this could result in a total dominance of recurrent excitation and top-down influences within the network-possibly resulting in the visual hallucinations reported after administration of high doses of muscarinic cholinergic antagonists [119,123].…”

Retrieval and Reconsolidation: Toward a Neurobiology of Remembering

“…There is an extensive literature on postsynaptic effects of NA in sensory pathways, with several investigators suggesting that NA increases signal/noise by inhibiting background neuronal firing while sparing evoked activity (Foote et al 1975;Waterhouse and Woodward 1980;Hasselmo et al 1997) or tuning sensory responses by narrowing the receptive field of sensory neurons (Waterhouse et al 1990; Figure 3 LC unit response to the conditioning context.Rats are trained to discriminate between tones of different frequencies, one of which is associated with a foot shock (CS+) and the other not (CS−). Two seconds before the presentation of either tone, a flashing light comes on and continues for the duration of the tone (2 sec).…”

Coactivation of M1Muscarinic and α1 Adrenergic Receptors Stimulates Extracellular Signal-Regulated Protein Kinase and Induces Long-Term Depression at CA3–CA1 Synapses in Rat Hippocampus

“…It is thought that during slow-wave sleep, lowered hippocampal ACh optimizes memory consolidation by releasing suppression of excitatory feedback connections (Kafka et al, 1986;Hasselmo, 1999). However, during REM sleep, when ACh is elevated in hippocampus, but both ACh and NE levels are low in cortex, activity is allowed to spread in cortex without hippocampal interference (Kafka et al, 1986;Dodt et al, 1991;Jones, 1991;Hasselmo et al, 1997;Hasselmo, 1999). Thus, hippocampal mLTD and NE LTD could potentially contribute to memory encoding, to memory consolidation during sleep, or both.…”