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1.
Psychopharmacology (Berl) ; 238(12): 3615-3627, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34546404

RESUMEN

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.


Asunto(s)
Neuronas Adrenérgicas , Receptores Adrenérgicos beta , Neuronas Adrenérgicas/metabolismo , Animales , Locus Coeruleus/metabolismo , Norepinefrina , Corteza Visual Primaria , Ratas
2.
Neurobiol Learn Mem ; 183: 107484, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34175450

RESUMEN

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.


Asunto(s)
Acetilcolina/metabolismo , Núcleo Basal de Meynert/fisiología , Neuronas Colinérgicas/fisiología , Recuerdo Mental/fisiología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Animales , Anticuerpos Monoclonales/farmacología , Núcleo Basal de Meynert/efectos de los fármacos , Núcleo Basal de Meynert/metabolismo , Colinérgicos/farmacología , Neuronas Colinérgicas/efectos de los fármacos , Neuronas Colinérgicas/metabolismo , Inhibidores de la Colinesterasa/farmacología , Donepezilo/farmacología , Recuerdo Mental/efectos de los fármacos , Neocórtex/efectos de los fármacos , Neocórtex/metabolismo , Neocórtex/fisiología , Ratas , Saporinas/farmacología
3.
PLoS One ; 15(3): e0230367, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32191757

RESUMEN

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.


Asunto(s)
Conducta Animal/efectos de los fármacos , Sensibilidad de Contraste/efectos de los fármacos , Movimiento/fisiología , Serotonina/farmacología , Animales , Ingestión de Líquidos , Masculino , Ratas Long-Evans
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