Noradrenaline modulates neuronal and perceptual visual detectability via ß-adrenergic receptor.

RATIONALE: Noradrenaline (NA) is a neuromodulator secreted from noradrenergic neurons in the locus coeruleus to the whole brain depending on the physiological state and behavioral context. It regulates various brain functions including vision via three major adrenergic receptor (AR) subtypes. Previous studies investigating the noradrenergic modulations on vision reported different effects, including improvement and impairment of perceptual visual sensitivity in rodents via ß-AR, an AR subtype. Therefore, it remains unknown how NA affects perceptual visual sensitivity via ß-AR and what neuronal mechanisms underlie it. OBJECTIVES: The current study investigated the noradrenergic modulation of perceptual and neuronal visual sensitivity via ß-AR in the primary visual cortex (V1). METHODS: We performed extracellular multi-point recordings from V1 of rats performing a go/no-go visual detection task under the head-fixed condition. A ß-AR blocker, propranolol (10 mM), was topically administered onto the V1 surface, and the drug effect on behavioral and neuronal activities was quantified by comparing pre-and post-drug administration. RESULTS: The topical administration of propranolol onto the V1 surface significantly improved the task performance. An analysis of the multi-unit activity in V1 showed that propranolol significantly suppressed spontaneous activity and facilitated the visual response of the recording sites in V1. We further calculated the signal-to-noise ratio (SNR), finding that the SNR was significantly improved after propranolol administration. CONCLUSIONS: Pharmacological blockade of ß-AR in V1 improves perceptual visual detectability by modifying the SNR of neuronal activity.

Acetylcholine from the nucleus basalis magnocellularis facilitates the retrieval of well-established memory.

Retrieval deficit of long-term memory is a cardinal symptom of dementia and has been proposed to associate with abnormalities in the central cholinergic system. Difficulty in the retrieval of memory is experienced by healthy individuals and not limited to patients with neurological disorders that result in forgetfulness. The difficulty of retrieving memories is associated with various factors, such as how often the event was experienced or remembered, but it is unclear how the cholinergic system plays a role in the retrieval of memory formed by a daily routine (accumulated experience). To investigate this point, we trained rats moderately (for a week) or extensively (for a month) to detect a visual cue in a two-alternative forced-choice task. First, we confirmed the well-established memory in the extensively trained group was more resistant to the retrieval problem than recently acquired memory in the moderately trained group. Next, we tested the effect of a cholinesterase inhibitor, donepezil, on the retrieval of memory after a long no-task period in extensively trained rats. Pre-administration of donepezil improved performance and reduced the latency of task initiation compared to the saline-treated group. Finally, we lesioned cholinergic neurons of the nucleus basalis magnocellularis (NBM), which project to the entire neocortex, by injecting the cholinergic toxin 192 IgG-saporin. NBM-lesioned rats showed severely impaired task initiation and performance. These abilities recovered as the trials progressed, though they never reached the level observed in rats with intact NBM. These results suggest that acetylcholine released from the NBM contributes to the retrieval of well-established memory developed by a daily routine.

Serotonin improves behavioral contrast sensitivity of freely moving rats.

Serotonin (5-HT) is a neuromodulator secreted from serotonergic neurons located in the pons and upper brain stem in a behavioral context-dependent manner. The serotonergic axon terminals innervate almost the whole brain, causing modulatory actions on various brain functions including vision. Our previous study demonstrated the visual responses of neurons in the primary visual cortex (V1) of anesthetized monkeys were modulated by the activation of 5-HT receptors depending on the response magnitude, in which 5-HT2A receptor-selective agonists enhanced weak visual responses but not strong responses. This observation suggests that the activation of serotonergic receptors modulates neuronal visual information processing to improve the behavioral detectability of a stimulus. However, it remains unknown if 5-HT improves visual detectability at the behavioral level. To investigate this point, visual detectability was measured as contrast sensitivity (CS) in freely moving rats using a two-alternative forced-choice visual detection task (2AFC-VDT) combined with the staircase method. The grating contrast was decreased or increased step by step after a correct choice (hit) or incorrect choice (miss), respectively. CS was evaluated as an inverse value of the visual contrast threshold. The effect of the intraperitoneal administration of fluoxetine (FLX, 5 mg/kg), a selective serotonin reuptake inhibitor, on CS was tested. The CS of rats was significantly higher in FLX than control conditions, and the drug effect showed specificity for the spatial frequency (SF) of a grating stimulus, in which CS improvement was observed at optimal SF but not non-optimal high SF. Thus, we conclude that endogenously-secreted serotonin in the brain improves visual detectability, which may be mediated by vision-related neurons acquiring SF information of the visual stimulus.

Caffeine improves contrast sensitivity of freely moving rats.

Caffeine (1, 3, 7-trimethylxanthine) is a well-known central nervous system stimulant that affects various brain functions such as attention, memory and sensation. However, it remains unclear whether and how caffeine modulates visual ability such as contrast sensitivity (CS) and the CS-spatial frequency (SF) relationship. To investigate these points, we tested the effects of caffeine on the perceptual CS of rats under three SF conditions. CS was measured using a two-alternative forced choice (2AFC) grating detection task combined with a staircase method. Intraperitoneal administration of caffeine 30 min prior to the task improved CS in an SF-dependent manner, in which the improving effect was observed at 0.1 cycles/degree (cpd) of the optimal SF for rats but not at 0.5 or 1 cpd. We concluded that caffeine, a representative ingredient contained in foods or drinks consumed daily, leads to an improvement of perceptual visual sensitivity.

Cholinergic and serotonergic modulation of visual information processing in monkey V1.

The brain dynamically changes its input-output relationship depending on the behavioral state and context in order to optimize information processing. At the molecular level, cholinergic/monoaminergic transmitters have been extensively studied as key players for the state/context-dependent modulation of brain function. In this paper, we review how cortical visual information processing in the primary visual cortex (V1) of macaque monkey, which has a highly differentiated laminar structure, is optimized by serotonergic and cholinergic systems by examining anatomical and in vivo electrophysiological aspects to highlight their similarities and distinctions. We show that these two systems have a similar layer bias for axonal fiber innervation and receptor distribution. The common target sites are the geniculorecipient layers and geniculocortical fibers, where the appropriate gain control is established through a geniculocortical signal transformation. Both systems exert activity-dependent response gain control across layers, but in a manner consistent with the receptor subtype. The serotonergic receptors 5-HT1B and 5HT2A modulate the contrast-response curve in a manner consistent with bi-directional response gain control, where the sign (facilitation/suppression) is switched according to the firing rate and is complementary to the other. On the other hand, cholinergic nicotinic/muscarinic receptors exert mono-directional response gain control without a sign reversal. Nicotinic receptors increase the response magnitude in a multiplicative manner, while muscarinic receptors exert both suppressive and facilitative effects. We discuss the implications of the two neuromodulator systems in hierarchical visual signal processing in V1 on the basis of the developed laminar structure.

Online estimation of a cognitive performance using heart rate variability.

This paper presents online estimation framework of a cognitive performance using heart rate variability (HRV). Although our former framework could estimate relative changes in one user's cognitive performance after it had finished measuring his/her HRV, it was unable to estimate a cognitive performance repeatedly or to compare the estimated results obtained for multiple users. To address these problems, we have developed a framework for online estimation of a cognitive performance. Experimental results show our framework estimates a cognitive performance more accurately than the previous study did using multiple vital sensors. It can also estimate a user's cognitive performance by comparing it with those estimated for others. It therefore has the potential to help managerial personnel monitor their workers' performances in real time to suggest rest periods or changes in work duties.