Ramelteon administration enhances novel object recognition and spatial working memory in mice.

Ramelteon is used to ameliorate sleep disorders that negatively affect memory performance; however, it remains unknown whether ramelteon strengthens neutral memories, which do not involve reward or punishment. To address this, we monitored behavior of mice treated with vehicle/ramelteon while they performed a novel object recognition task and a spontaneous alternation task. Object memory performance in the novel object recognition task was improved only if ramelteon was injected before training, suggesting that ramelteon specifically enhances the acquisition of object recognition memory. Ramelteon also enhanced spatial working memory in the spontaneous alternation task. Altogether, acute ramelteon treatment enhances memory in quasi-natural contexts.

An open-source application to identify the three-dimensional locations of electrodes implanted into the rat brain from computed tomography images.

Electrophysiological recordings using metal electrodes implanted into the brains have been widely utilized to evaluate neuronal circuit dynamics related to behavior and external stimuli. The most common method for identifying implanted electrode tracks in the brain tissue has been histological examination following postmortem slicing and staining of the brain tissue, which consumes time and resources and occasionally fails to identify the tracks because the brain preparations have been damaged during processing. Recent studies have proposed the use of a promising alternative method, consisting of computed tomography (CT) scanning that can directly reconstruct the three-dimensional arrangements of electrodes in the brains of living animals. In this study, we developed an open-source Python-based application that estimates the location of an implanted electrode from CT image sequences in a rat. After the user manually sets reference coordinates and an area from a sequence of CT images, this application automatically overlays an estimated location of an electrode tip on a histological template image; the estimates are highly accurate, with less than 135 µm of error, irrespective of the depth of the brain region. The estimation of an electrode location can be completed within a few minutes. Our simple and user-friendly application extends beyond currently available CT-based electrode localization methods and opens up the possibility of applying this technique to various electrophysiological recording paradigms.

Enhancement of Motor Cortical Gamma Oscillations and Sniffing Activity by Medial Forebrain Bundle Stimulation Precedes Locomotion.

The medial forebrain bundle (MFB) is a white matter pathway that traverses through mesolimbic structures and includes dopaminergic neural fibers ascending from the ventral tegmental area (VTA). Since dopaminergic signals represent hedonic responses, electrical stimulation of the MFB in animals has been used as a neural reward for operant and spatial tasks. MFB stimulation strongly motivates animals to rapidly learn to perform a variety of behavioral tasks to obtain a reward. Although the MFB is known to connect various brain regions and MFB stimulation dynamically modulates animal behavior, how central and peripheral functions are affected by MFB stimulation per se is poorly understood. To address this question, we simultaneously recorded electrocorticograms (ECoGs) in the primary motor cortex (M1), primary somatosensory cortex (S1), and olfactory bulb (OB) of behaving rats while electrically stimulating the MFB. We found that MFB stimulation increased the locomotor activity of rats. Spectral analysis confirmed that immediately after MFB stimulation, sniffing activity was facilitated and the power of gamma oscillations in the M1 was increased. After sniffing activity and motor cortical gamma oscillations were facilitated, animals started to move. These results provide insight into the importance of sniffing activity and cortical gamma oscillations for motor execution and learning facilitated by MFB stimulation.