Theta-phase-specific modulation of dentate gyrus memory neurons.

The theta rhythm, a quasi-periodic 4-10 Hz oscillation, is observed during memory processing in the hippocampus, with different phases of theta hypothesized to separate independent streams of information related to the encoding and recall of memories. At the cellular level, the discovery of hippocampal memory cells (engram neurons), as well as the modulation of memory recall through optogenetic activation of these cells, has provided evidence that certain memories are stored, in part, in a sparse ensemble of neurons in the hippocampus. In previous research, however, engram reactivation has been carried out using open-loop stimulation at fixed frequencies; the relationship between engram neuron reactivation and ongoing network oscillations has not been taken into consideration. To address this concern, we implemented a closed-loop reactivation of engram neurons that enabled phase-specific stimulation relative to theta oscillations in the local field potential in CA1. Using this real-time approach, we tested the impact of activating dentate gyrus engram neurons during the peak (encoding phase) and trough (recall phase) of theta oscillations. Consistent with previously hypothesized functions of theta oscillations in memory function, we show that stimulating dentate gyrus engram neurons at the trough of theta is more effective in eliciting behavioral recall than either fixed-frequency stimulation or stimulation at the peak of theta. Moreover, phase-specific trough stimulation is accompanied by an increase in the coupling between gamma and theta oscillations in CA1 hippocampus. Our results provide a causal link between phase-specific activation of engram cells and the behavioral expression of memory.

Outcomes following TORS for HPV-positive oropharyngeal carcinoma: PEGs, tracheostomies, and beyond.

OBJECTIVES: To review swallowing, airway and speech outcomes following transoral robotic surgery (TORS) ±â€¯adjuvant therapy for human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV[+]OPSCC). METHODS: Patients underwent TORS ± standard adjuvant therapy from 5/1/2007-5/31/2015. Clinical data were recorded and descriptive analysis was performed. RESULTS: 267 patients met criteria. All patients underwent surgery at Mayo, however, only 41/81 and 71/119 patients received RT and CRT at a Mayo Clinic site. A PEG was placed in 77 patients (3 prior to any treatment, 74 reactively during adjuvant therapy), with 3 PEG dependent and 3 partially PEG reliant at last follow-up. Tracheostomy was performed in 30 (11%) patients; 28 were decannulated. Swallow evaluations were completed for 20/81 undergoing RT and 50/119 undergoing CRT at a median of 3.8 and 7.6 months post-treatment, respectively. An unrestricted oral diet was reported by 5% following RT and 12% following CRT on the Functional Oral Intake Scale. HN-PSS normalcy of diet scores indicated a diet beyond soft chewable foods for 27% following RT and 46% following CRT. No restriction of place, food, or companion was reported for the HN-PSS for public eating in 13% after RT and 33% after CRT. Aspiration of thin liquid was present in 17% and 28% following RT and CRT, respectively. HN-PSS understandability of speech was "always understandable" in 60% and 63%, following RT and CRT, respectively. Hoarseness was reported in 56% and 45% following RT and CRT respectively. CONCLUSION: Long-term PEG and tracheostomy dependence in this cohort is low. However, these outcomes under-represent the decrement in patient speech and swallowing following TORS ± standard adjuvant therapy for HPV(+)OPSCC.