Summary The hippocampal CA3 region is classically viewed as a homogeneous autoassociative network critical for associative memory and pattern completion. However, recent evidence has demonstrated a striking heterogeneity along the transverse, or proximodistal, axis of CA3 in spatial encoding and memory. Here we report the presence of striking proximodistal gradients in intrinsic membrane properties and synaptic connectivity for dorsal CA3. A decreasing gradient of mossy fiber synaptic strength along the proximodistal axis is mirrored by an increasing gradient of direct synaptic excitation from entorhinal cortex. Furthermore, we uncovered a nonuniform pattern of reactivation of fear memory traces, with the most robust reactivation during memory retrieval occurring in mid-CA3 (CA3b), the region showing the strongest net recurrent excitation. Our results suggest that heterogeneity in both intrinsic properties and synaptic connectivity may contribute to the distinct spatial encoding and behavioral role of CA3 subregions along the proximodistal axis.

No abstract

Recent studies have focused on the identification and manipulation of memory traces in rodent models. The two main mouse models utilized are either a CreERT2/loxP tamoxifen (TAM)- or a tetracycline transactivator (tTA)/tetracycline-response element (TRE) doxycycline (DOX)-inducible system. These systems, however, could be improved to label a more specific population of activated neurons corresponding to behavior. Here, we sought to identify an improved selective estrogen receptor (ER) modulator (SERM) in which we could label an individual memory trace in ArcCreERT2 mice. We found that 4-hydroxytamoxifen (4-OHT) is the most selective SERM in the ArcCreERT2 x ROSA26-CAG-stopflox-channelrhodospin (ChR2)-enhanced yellow fluorescent protein (eYFP) mice. The half-life of 4-OHT is also shorter than TAM, allowing for more specificity of memory trace labeling. Furthermore, 4-OHT allowed for context-specific labeling in the dentate gyrus (DG) and CA3. In summary, we believe 4-OHT improves the specificity of memory trace labeling and will allow for refined memory trace studies in the future.

Study Design: Retrospective database study.Objective: To analyze the economic and age data concerning primary and revision posterolateral fusion (PLF) and posterior/ transforaminal lumbar interbody fusion (PLIF/TLIF) throughout the United States to improve value-based care and health care utilization. Methods:The National Inpatient Sample (NIS) database was queried by the International Classification of Diseases, Ninth Revision, Clinical Modification codes for patients who underwent primary or revision PLF and PLIF/TLIF between 2011 and 2014. Age and economic data included number of procedures, costs, and revision burden. The National Inpatient Sample database represents a 20% sample of discharges from US hospitals weighted to provide national estimates. Results: From 2011 to 2014, the annual number of PLF and PLIF/TLIF procedures decreased 18% and increased 23%, respectively, in the Unites States. During the same period, the number of revision PLF decreased 19%, while revision PLIF/TLIF remained relatively unchanged. The average cost of PLF was lower than the average cost of PLIF/TLIF. The aggregate national cost for PLF was more than $3 billion, while PLIF/TLIF totaled less than $2 billion. Revision burden (ratio of revision surgeries to the sum of both revision and primary surgeries) remained constant at 8.0% for PLF while it declined from 3.2% to 2.9% for PLIF/TLIF. Conclusion: This study demonstrated a steady increase in PLIF/TLIF, while PLF alone decreased. The increasing number of PLIF/ TLIF procedures may account for the apparent decline of PLF procedures. There was a higher average cost for PLIF/TLIF as compared with PLF. Revision burden remained unchanged for PLF but declined for PLIF/TLIF, implying a decreased need for revision procedures following the initial PLIF/TLIF surgery.