Heterogeneity in Kv2 Channel Expression Shapes Action Potential Characteristics and Firing Patterns in CA1 versus CA2 Hippocampal Pyramidal Neurons.

The CA1 region of the hippocampus plays a critical role in spatial and contextual memory, and has well-established circuitry, function and plasticity. In contrast, the properties of the flanking CA2 pyramidal neurons (PNs), important for social memory, and lacking CA1-like plasticity, remain relatively understudied. In particular, little is known regarding the expression of voltage-gated K+ (Kv) channels and the contribution of these channels to the distinct properties of intrinsic excitability, action potential (AP) waveform, firing patterns and neurotransmission between CA1 and CA2 PNs. In the present study, we used multiplex fluorescence immunolabeling of mouse brain sections, and whole-cell recordings in acute mouse brain slices, to define the role of heterogeneous expression of Kv2 family Kv channels in CA1 versus CA2 pyramidal cell excitability. Our results show that the somatodendritic delayed rectifier Kv channel subunits Kv2.1, Kv2.2, and their auxiliary subunit AMIGO-1 have region-specific differences in expression in PNs, with the highest expression levels in CA1, a sharp decrease at the CA1-CA2 boundary, and significantly reduced levels in CA2 neurons. PNs in CA1 exhibit a robust contribution of Guangxitoxin-1E-sensitive Kv2-based delayed rectifier current to AP shape and after-hyperpolarization potential (AHP) relative to that seen in CA2 PNs. Our results indicate that robust Kv2 channel expression confers a distinct pattern of intrinsic excitability to CA1 PNs, potentially contributing to their different roles in hippocampal network function

The significance of female imagery in the book of Proverbs wisdom and wife compared

This thesis is an examination of parallel female imagery found in the Book of Proverbs, specifically that of Wisdom personified (Chapters 1-9) and the ideal wife (31:10-31). A discussion of their common traits is based on criteria taken directly from the literary text. A brief discourse introduces the reader to the problematic dating of the poetic forms in Proverbs. The main body of the thesis details the various categories of comparison: direct literal parallels, literal and thematic parallels, thematic parallels and differences. The primary aim of this study is to determine the importance of these many points of comparison, to analyze these comparisons, and to discover their significance. The last section of this thesis shows how the Wisdom/wife parallels provided an insight into the relationship men had with Wisdom and with God. This was done by relating that relationship with the one a husband had with his wife

Relationship between Pore Occupancy and Gating in BK Potassium Channels

Permeant ions can have significant effects on ion channel conformational changes. To further understand the relationship between ion occupancy and gating conformational changes, we have studied macroscopic and single-channel gating of BK potassium channels with different permeant monovalent cations. While the slopes of the conductance–voltage curve were reduced with respect to potassium for all permeant ions, BK channels required stronger depolarization to open only when thallium was the permeant ion. Thallium also slowed the activation and deactivation kinetics. Both the change in kinetics and the shift in the GV curve were dependent on the thallium passing through the permeation pathway, as well as on the concentration of thallium. There was a decrease in the mean open time and an increase in the number of short flicker closing events with thallium as the permeating ion. Mean closed durations were unaffected. Application of previously established allosteric gating models indicated that thallium specifically alters the opening and closing transition of the channel and does not alter the calcium activation or voltage activation pathways. Addition of a closed flicker state into the allosteric model can account for the effect of thallium on gating. Consideration of the thallium concentration dependence of the gating effects suggests that the flicker state may correspond to the collapsed selectivity filter seen in crystal structures of the KcsA potassium channel under the condition of low permeant ion concentration

A new class of continuous-time delay- compensated parameter-varying low-pass elliptic filters with improved dynamic behavior

In some applications, it is required to have continuous- time low-pass analog filtering systems which simultaneously possess a constant group delay in the passband and a narrow transition band. Usually, these systems are implemented by adding to the output of a filter with steep-amplitude selectivity (an elliptic filter, for instance) an all-pass filter which compensates the unfavorable run of the group delay response of the first filter. However, this compensation process will also increase the duration of the transient response of the resulting filtering system. This paper presents a new class of delay-compensated parameter-varying lowpass elliptic filters with a transient response of short duration. This improvement is achieved by means of a temporary change in the value of the filter parameters when a steplike transition with a minimum amplitude is detected in the input signal. As a consequence of the control strategy used to induce parameter variations in the proposed class of filters, its behavior is nonlinear in nature. Therefore, its stability properties (and particularly their bounded-input bounded-output stability) are also assessed. Simulations verifying the effectiveness of the new class of filters are presented and compared to the performance of delay-compensated and delay-uncompensated elliptic filters which were chosen as study cases

Hippocampal area CA2: interneuron disfunction during pathological states

Hippocampal area CA2 plays a critical role in social recognition memory and has unique cellular and molecular properties that distinguish it from areas CA1 and CA3. In addition to having a particularly high density of interneurons, the inhibitory transmission in this region displays two distinct forms of long-term synaptic plasticity. Early studies on human hippocampal tissue have reported unique alteration in area CA2 with several pathologies and psychiatric disorders. In this review, we present recent studies revealing changes in inhibitory transmission and plasticity of area CA2 in mouse models of multiple sclerosis, autism spectrum disorder, Alzheimer’s disease, schizophrenia and the 22q11.2 deletion syndrome and propose how these changes could underly deficits in social cognition observed during these pathologies

Community–Based Dental Education and Dentists’ Attitudes and Behavior Concerning Patients from Underserved Populations

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153650/1/jddj002203372014781tb05663x.pd

Dental School and Community Clinic Financial Arrangements

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153602/1/jddj0022033720117510suppltb05194x.pd

Unambiguous observation of blocked states reveals altered, blocker-induced, cardiac ryanodine receptor gating

The flow of ions through membrane channels is precisely regulated by gates. The architecture and function of these elements have been studied extensively, shedding light on the mechanisms underlying gating. Recent investigations have focused on ion occupancy of the channel’s selectivity filter and its ability to alter gating, with most studies involving prokaryotic K+ channels. Some studies used large quaternary ammonium blocker molecules to examine the effects of altered ionic flux on gating. However, the absence of blocking events that are visibly distinct from closing events in K+ channels makes unambiguous interpretation of data from single channel recordings difficult. In this study, the large K+ conductance of the RyR2 channel permits direct observation of blocking events as distinct subconductance states and for the first time demonstrates the differential effects of blocker molecules on channel gating. This experimental platform provides valuable insights into mechanisms of blocker-induced modulation of ion channel gating

Development of a Sustainable Community‐Based Dental Education Program

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153534/1/jddj002203372011758tb05148x.pd