Electrophysiology and Morphology of Human Cortical Supragranular Pyramidal Cells in a Wide Age Range.

The basic excitatory neurons of the cerebral cortex, the pyramidal cells, are the most important signal integrators for the local circuit. They have quite characteristic morphological and electrophysiological properties that are known to be largely constant with age in the young and adult cortex. However, the brain undergoes several dynamic changes throughout life, such as in the phases of early development and cognitive decline in the aging brain. We set out to search for intrinsic cellular changes in supragranular pyramidal cells across a broad age range: from birth to 85 years of age and we found differences in several biophysical properties between defined age groups. During the first year of life, subthreshold and suprathreshold electrophysiological properties changed in a way that shows that pyramidal cells become less excitable with maturation, but also become temporarily more precise. According to our findings, the morphological features of the three-dimensional reconstructions from different life stages showed consistent morphological properties and systematic dendritic spine analysis of an infantile and an old pyramidal cell showed clear significant differences in the distribution of spine shapes. Overall, the changes that occur during development and aging may have lasting effects on the properties of pyramidal cells in the cerebral cortex. Understanding these changes is important to unravel the complex mechanisms underlying brain development, cognition and age-related neurodegenerative diseases.

Temporal disparity of action potentials triggered in axon initial segments and distal axons in the neocortex.

Neural population activity determines the timing of synaptic inputs, which arrive to dendrites, cell bodies, and axon initial segments (AISs) of cortical neurons. Action potential initiation in the AIS (AIS-APs) is driven by input integration, and the phase preference of AIS-APs during network oscillations is characteristic to cell classes. Distal regions of cortical axons do not receive synaptic inputs, yet experimental induction protocols can trigger retroaxonal action potentials (RA-APs) in axons distal from the soma. We report spontaneously occurring RA-APs in human and rodent cortical interneurons that appear uncorrelated to inputs and population activity. Network-linked triggering of AIS-APs versus input-independent timing of RA-APs of the same interneurons results in disparate temporal contribution of a single cell to in vivo network operation through perisomatic and distal axonal firing.

Multimorbidity is associated with uptake of influenza vaccination.

OBJECTIVE: Patients with chronic conditions have higher rates of severe influenza-related illness and mortality. However, influenza vaccination coverage in high-risk populations continues to be suboptimal. We describe the association between cumulative disease morbidity, measured by a previously validated multimorbidity index, and influenza vaccination among community-dwelling adults. METHODS: We obtained interview and medical record data for participants  ≥18 years who sought outpatient care for influenza-like illness between 2011 and 2016 as part of an outpatient-based study of influenza vaccine effectiveness. We defined cumulative disease morbidity by using medical diagnosis codes to calculate a multimorbidity-weighted index (MWI) for each participant. MWI and influenza vaccination status was evaluated by logistic regression. Akaike information criterion was calculated for all models. RESULTS: Overall, 1458 (48%) of participants out of a total of 3033 received influenza vaccination. The median MWI was 0.9 (IQR 0.00-3.5) and was higher among vaccinated participants (median 1.6 versus 0.0; p < 0.001). We found a positive linear association between MWI and vaccination, and vaccination percentages were compared between categories of MWI. Compared to patients with no multimorbidity (MWI = 0), odds of vaccination were 17% higher in the second category (MWI 0.01-1.50; [OR: 1.17, 95% CI: 0.92-1.50]), 58% higher in the third category (MWI 1.51-3.00; [OR: 1.58, 95% CI: 1.26-1.99]), 130% higher in the fourth category (MWI 3.01-6.00; [OR: 2.30, 95% CI: 1.78-2.98]) and 214% higher in the fifth category (MWI 6.01-45.00;[OR: 3.14, 95% CI: 2.41-4.10]). Participants defined as high-risk had 86% greater odds of being vaccinated than non-high-risk individuals (OR: 1.86, 95% CI: 1.56-2.21). The AIC was lowest for MWI compared with high-risk conditions. CONCLUSIONS: Our results suggest a dose response relationship between level of multimorbidity and likelihood of influenza vaccination. Compared with high-risk condition designations, MWI provided improved precision and a better model fit for the measurement of chronic disease and influenza vaccination.