The hippocampus supports high-precision binding in visual working memory.

It is well established that the hippocampus is critical for long-term episodic memory, but a growing body of research suggests that it also plays a critical role in supporting memory over very brief delays as measured in tests of working memory (WM). However, the circumstances under which the hippocampus is necessary for WM and the specific processes that it supports remain controversial. We propose that the hippocampus supports WM by binding together high-precision properties of an event, and we test this claim by examining the precision of color-location bindings in a visual WM task in which participants report the precise color of studied items using a continuous color wheel. Amnestic patients with hippocampal damage were significantly impaired at retrieving these colors after a 1-s delay, and these impairments reflected a reduction in the precision of those memories rather than increases in total memory failures or binding errors. Moreover, a parallel fMRI study in healthy subjects revealed that neural activity in the head and body of the hippocampus was directly related to the precision of visual WM decisions. Together, these results indicate that the hippocampus is critical in complex high-precision binding that supports memory over brief delays.

The hippocampus is particularly important for building associations across stimulus domains.

The medial temporal lobe (MTL) is critical for binding together different attributes that together form memory for prior episodes, but whether it is preferentially involved in supporting specific types of associations is a topic of much debate. Some have argued that the MTL, specifically the hippocampus, may be specialized for binding information from different stimulus domains (e.g., linking visual and auditory stimuli). In the current study, we examined the role of the MTL in memory for associations within- vs. across-domains. Patients with either selective hippocampal lesions or more extensive MTL lesions studied pairs of items within the same stimulus domain (i.e., image-image or sound-sound pairs) or across different domains (i.e., image-sound pairs). Associative memory was subsequently tested by having participants discriminate between previously studied and rearranged pairs. Compared to healthy controls, the patients were significantly more impaired in the across-domain condition than the within-domain conditions. Similar deficits were observed for patients with hippocampal lesions and those with more extensive MTL lesions, suggesting that the hippocampus itself is particularly important for binding associations across stimulus domains.

Visual short-term memory for high resolution associations is impaired in patients with medial temporal lobe damage.

The medial temporal lobe (MTL) plays a critical role in episodic long-term memory, but whether the MTL is necessary for visual short-term memory is controversial. Some studies have indicated that MTL damage disrupts visual short-term memory performance whereas other studies have failed to find such evidence. To account for these mixed results, it has been proposed that the hippocampus is critical in supporting short-term memory for high resolution complex bindings, while the cortex is sufficient to support simple, low resolution bindings. This hypothesis was tested in the current study by assessing visual short-term memory in patients with damage to the MTL and controls for high resolution and low resolution object-location and object-color associations. In the location tests, participants encoded sets of two or four objects in different locations on the screen. After each set, participants performed a two-alternative forced-choice task in which they were required to discriminate the object in the target location from the object in a high or low resolution lure location (i.e., the object locations were very close or far away from the target location, respectively). Similarly, in the color tests, participants were presented with sets of two or four objects in a different color and, after each set, were required to discriminate the object in the target color from the object in a high or low resolution lure color (i.e., the lure color was very similar or very different, respectively, to the studied color). The patients were significantly impaired in visual short-term memory, but importantly, they were more impaired for high resolution object-location and object-color bindings. The results are consistent with the proposal that the hippocampus plays a critical role in forming and maintaining complex, high resolution bindings. © 2016 Wiley Periodicals, Inc.

Impairments in precision, rather than spatial strategy, characterize performance on the virtual Morris Water Maze: A case study.

Damage to the medial temporal lobes produces profound amnesia, greatly impairing the ability of patients to learn about new associations and events. While studies in rodents suggest a strong link between damage to the hippocampus and the ability to navigate using distal landmarks in a spatial environment, the connection between navigation and memory in humans remains less clear. Past studies on human navigation have provided mixed findings about whether patients with damage to the medial temporal lobes can successfully acquire and navigate new spatial environments, possibly due, in part, to issues related to patient demographics and characterization of medial temporal lobe damage. Here, we report findings from a young, high functioning patient who suffered severe medial temporal lobe damage. Although the patient is densely amnestic, her ability to acquire and utilize new, but coarse, spatial "maps" appears largely intact. Specifically, a novel computational analysis focused on the precision of her spatial search revealed a significant deficit in spatial precision rather than spatial search strategy. These findings argue that an intact hippocampus in humans is not necessary for representing multiple external landmarks during spatial navigation of new environments. We suggest instead that the human hippocampus may store and represent complex high-resolution bindings of features in the environment as part of a larger role in perception, memory, and navigation.

Proliferating reactive astrocytes are regulated by Notch-1 in the peri-infarct area after stroke.

BACKGROUND AND PURPOSE: The formation of reactive astrocytes is common after central nervous system injuries such as stroke. However, the signaling pathway(s) that control astrocyte formation and functions are poorly defined. We assess the effects of Notch 1 signaling in peri-infarct-reactive astrocytes after stroke. METHODS: We examined reactive astrocyte formation in the peri-infarct area 3 days after distal middle cerebral artery occlusion with or without γ-secretase inhibitor treatment. To directly study the effects of inhibiting a γ-secretase cleavage target in reactive astrocytes, we generated glial fibrillary acidic protein-CreER™:Notch 1 conditional knockout mice. RESULTS: Gamma-secretase inhibitor treatment after stroke decreased the number of proliferative glial fibrillary acidic protein-positive reactive astrocytes and RC2-positive reactive astrocytes directly adjacent to the infarct core. The decrease in reactive astrocytes correlated with an increased number of CD45-positive cells that invaded into the peri-infarct area. To study the influence of reactive astrocytes on immune cell invasion, ex vivo immune cell invasion assays were performed. We found that a γ-secretase-mediated pathway in astrocytes affected Jurkat cell invasion. After tamoxifen treatment, glial fibrillary acidic protein-CreER™:Notch 1 conditional knockout mice had a significantly decreased number of proliferating reactive astrocytes and RC2-positive reactive astrocytes. Tamoxifen treatment also led to an increased number of CD45-positive cells that invaded the peri-infarct area. CONCLUSIONS: Our results demonstrate that proliferating and RC2-positive reactive astrocytes are regulated by Notch 1 signal transduction and control immune cell invasion after stroke.