Cognitive Enhancement Mediated Through Postsynaptic Actions of Norepinephrine on Ongoing Cortical Activity

Abstract

We propose two distinct types of norepinephrine (NE)-neuromodulatory systems: an enhanced-excitatory and enhanced-inhibitory (E-E/E-I) system and a depressed-excitatory and enhanced-inhibitory (D-E/E-I) system. In both systems, inhibitory synaptic efficacies are enhanced, but excitatory ones are modified in a contradictory manner: the E-E/E-I system enhances excitatory synaptic efficacies, whereas the D-E/E-I system depresses them. The E-E/E-I and D-E/E-I systems altered the dynamic property of ongoing (background) neuronal activity and greatly influenced the cognitive performance (S/N ratio) of a cortical neural network. The E-E/E-I system effectively enhanced S/N ratio for weaker stimuli with lower doses of NE, whereas the D-E/E-I system enhanced stronger stimuli with higher doses of NE. The neural network effectively responded to weaker stimuli if brief gamma-bursts were involved in ongoing neuronal activity that is controlled under the E-E/E-I neuromodulatory system. If the E-E/E-I and the D-E/E-I systems interact within the neural network, depressed neurons whose activity is depressed by NE application have bimodal property. That is, S/N ratio can be enhanced not only for stronger stimuli as its original property but also for weaker stimuli, for which coincidental neuronal firings among enhanced neurons whose activity is enhanced by NE application are essential. We suggest that the recruitment of the depressed neurons for the detection of weaker (subthreshold) stimuli might be advantageous for the brain to cope with a variety of sensory stimuli.

Coherent ongoing subthreshold state of a cortical neural network regulated by slow- and fast-spiking interneurons

“…Our previous study (Hoshino 2005) proposed a network model with excitatory and inhibitory synapses between integrate-and-fire neurons that generate action potentials in a stochastic manner as in the present study. Synaptic efficacy was modulated by a neuromodulator known as norepinephrine.…”

“…Previous studies (van Vreeswijk & Sompolinsky 1996Hoshino 2005) demonstrated that synaptic balance between excitation and inhibition is crucial for coordinating ongoing spontaneous neuronal activity. van Sompolinsky (1996, 1998) proposed a network model consisting of excitatory and inhibitory populations of binary neurons.…”

Neuromodulation of distributed neural networks by tonic and phasic release of norepinephrine

“…The previous study [2] proposed an early sensory cortical model, in which the efficacy of excitatory and inhibitory synaptic transmissions was modulated depending on the level of NE in the network. The study showed that NE regulates a balance in efficacy between excitatory and inhibitory synaptic transmission, by which S/N (signal-to-noise) ratio was enhanced.…”

“…The locus coeruleus (LC) is believed to be involved in the 0531 regulation of cognitive information processing, in which the release of norepinephrine (NE) through rich efferent projections into relevant cortical areas plays an important role [1]. In a previous study [2], using a single cortical neural network model I have demonstrated that the LC-NE system effectively enhances signal-to-noise (S/N) ratio for weaker stimuli.…”

An Ongoing Subthreshold Neuronal State Established Through Dynamic Coassembling of Cortical Cells

“…The network has ongoing (spontaneous) neuronal activity, where individual dynamic core and noncore cell assemblies could emerge as attractors in the network dynamics in a temporal and random manner (Hoshino, Kashimori, & Kambara, 1996;Hoshino, Usuba, Kashimori, & Kambara, 1997;Hoshino, Inoue, Kashimori, & Kambara, 2001;Hoshino, Zheng, & Kuroiwa, 2003;Hoshino, 2004Hoshino, , 2005Hoshino, , 2006. Transient dynamic linking between the core and one of the noncore cell assemblies, called dynamic coassembling here, frequently and randomly takes place during the ongoing period.…”