Long-term depression of excitatory transmission in the lateral septum.

Neurons in the lateral septum (LS) integrate glutamatergic synaptic inputs, primarily from hippocampus, and send inhibitory projections to brain regions involved in reward and the generation of motivated behavior. Motivated learning and drugs of abuse have been shown to induce long-term changes in the strength of glutamatergic synapses in the LS, but the cellular mechanisms underlying long-term synaptic modification in the LS are poorly understood. Here, we examined synaptic transmission and long-term depression (LTD) in brain slices prepared from male and female C57BL/6 mice. No sex differences were observed in whole cell patch-clamp recordings of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R)- and N-methyl-d-aspartate receptor (NMDA-R)-mediated currents. Low-frequency stimulation of the fimbria fiber bundle (1 Hz 15 min) induced LTD of the LS field excitatory postsynaptic potential (fEPSP). Induction of LTD was blocked by the NMDA-R antagonist (d)-2-amino-5-phosphonovaleric acid (APV), but not the selective antagonist of GluN2B-containing NMDA-Rs ifenprodil. These results demonstrate the NMDA-R dependence of LTD in the LS. The LS is a sexually dimorphic structure, and sex differences in glutamatergic transmission have been reported in vivo; our results suggest sex differences observed in vivo result from network activity rather than intrinsic differences in glutamatergic transmission.NEW & NOTEWORTHY The lateral septum (LS) integrates information from hippocampus and other regions to provide context-dependent (top down or higher order) regulation of mood and motivated behavior. Learning and drugs of abuse induce long-term changes in the strength of glutamatergic projections to the LS; however, the cellular mechanisms underlying such changes are poorly understood. Here, we demonstrate there are no apparent sex differences in fast excitatory transmission and that long-term synaptic depression in the LS is NMDA-R dependent.

Optimizing Technology-Based Prompts for Supporting People Living With Dementia in Completing Activities of Daily Living at Home: Experimental Approach to Prompt Modality, Task Breakdown, and Attentional Support.

BACKGROUND: Assistive technology is becoming increasingly accessible and affordable for supporting people with dementia and their care partners living at home, with strong potential for technology-based prompting to assist with initiation and tracking of complex, multistep activities of daily living. However, there is limited direct comparison of different prompt features to guide optimal technology design. OBJECTIVE: Across 3 experiments, we investigated the features of tablet-based prompts that best support people with dementia to complete activities of daily living at home, measuring prompt effectiveness and gaining feedback from people with dementia and their care partners about their experiences. METHODS: Across experiments, we developed a specialized iPad app to enable data collection with people with dementia at home over an extended experimental period. In experiment 1, we varied the prompts in a 3 (visual type: text instruction, iconic image, and photographic image) × 3 (audio type: no sound, symbolic sound, and verbal instruction) experimental design using repeated measures across multiple testing sessions involving single-step activities. In experiment 2, we tested the most effective prompt breakdown for complex multistep tasks comparing 3 conditions (1-prompt, 3-prompt, and 7-prompt conditions). In experiment 3, we compared initiation and maintenance alerts that involved either an auditory tone or an auditory tone combined with a verbal instruction. Throughout, we asked people with dementia and their care partners to reflect on the usefulness of prompting technology in their everyday lives and what could be developed to better meet their needs. RESULTS: First, our results showed that audible verbal instructions were more useful for task completion than either tone-based or visual prompts. Second, a more granular breakdown of tasks was generally more useful and increased independent use, but this varied across individuals. Third, while a voice or text maintenance alert enabled people with dementia to persist with a multistep task for longer when it was more frequent, task initiation still frequently required support from a care partner. CONCLUSIONS: These findings can help inform developers of assistive technology about the design features that promote the usefulness of home prompting systems for people with dementia as well as the preferences and insights of people with dementia and their care partners regarding assistive technology design.