Altered Excitability and Local Connectivity of mPFC-PAG Neurons in a Mouse Model of Neuropathic Pain

The medial prefrontal cortex (mPFC) plays a major role in both sensory and affective aspects of pain. There is extensive evidence that chronic pain produces functional changes within the mPFC. However, our understanding of local circuit changes to defined subpopulations of mPFC neurons in chronic pain models remains unclear. A major subpopulation of mPFC neurons project to the periaqueductal gray (PAG), which is a key midbrain structure involved in endogenous pain suppression and facilitation. Here, we used laser scanning photostimulation of caged glutamate to map cortical circuits of retrogradely labeled cortico-PAG (CP) neurons in layer 5 (L5) of mPFC in brain slices prepared from male mice having undergone chronic constriction injury (CCI) of the sciatic nerve. Whole-cell recordings revealed a significant reduction in excitability for L5 CP neurons contralateral to CCI in the prelimbic (PL), but not infralimbic (IL), region of mPFC. Circuit mapping showed that excitatory inputs to L5 CP neurons in both PL and IL arose primarily from layer 2/3 (L2/3) and were significantly reduced in CCI mice. Glutamate stimulation of L2/3 and L5 elicited inhibitory inputs to CP neurons in both PL and IL, but only L2/3 input was significantly reduced in CP neurons of CCI mice. We also observed significant reduction in excitability and L2/3 inhibitory input to CP neurons ipsilateral to CCI. These results demonstrating region and laminar specific changes to mPFC-PAG neurons suggest that a unilateral CCI bilaterally alters cortical circuits upstream of the endogenous analgesic network, which may contribute to persistence of chronic pain

Highly differentiated cellular and circuit properties of infralimbic pyramidal neurons projecting to the periaqueductal gray and amygdala

The infralimbic (IL) cortex is a key node in an inter-connected network involved in fear and emotion processing. The cellular and circuit-level mechanisms whereby IL neurons receive, filter, and modulate incoming signals they project onward to diverse downstream nodes in this complex network remain poorly understood. Using the mouse as our model, we applied anatomical labeling strategies, brain slice electrophysiology, and focal activation of caged glutamate via laser scanning photostimulation (glu-LSPS) for quantitative neurophysiological analysis of projectionally defined neurons in IL. Injection of retrograde tracers into the periaqueductal gray (PAG) and basolateral amygdala (BLA) was used to identify cortico-PAG (CP) and cortico-BLA (CA) neurons in IL. CP neurons were found exclusively in layer 5 (L5) of IL whereas CA neurons were detected throughout layer 2, 3, and 5 of IL. We also identified a small percentage of IL neurons that project to both the PAG and the BLA. We found that L5 CP neurons have a more extensive dendritic structure compared to L5 CA neurons. Neurophysiological recordings performed on retrogradely labeled neurons in acute brain slice showed that CP and CA neurons in IL could be broadly classified in two groups: neuronal resonators and non-resonators. Layer 2 CA neurons were the only class that was exclusively non-resonating. CP, CA, and CP/CA neurons in layers 3 and 5 of IL consisted of heterogeneous populations of resonators and non-resonators showing that projection target is not an exclusive predictor of intrinsic physiology. Circuit mapping using glu-LSPS revealed that the strength and organization of local excitatory and inhibitory inputs were stronger to CP compared to CA neurons in IL. Together, our results establish an organizational scheme linking cellular neurophysiology with microcircuit parameters of defined neuronal subclasses in IL that send descending commands to subcortical structures involved in fear behavior

A Summary Report of Pink Bollworm Research in 1965

This item is part of the Agricultural Experiment Station archive. It was digitized from a physical copy provided by the University Libraries at the University of Arizona. For more information, please email CALS Publications at [email protected]

Interdisciplinary Collaboration Needed in Obtaining High-Quality Medical Information in Child Abuse Investigations

Background Despite reporting legislation, healthcare providers (HCPs) do not always report and collaborate in cases of suspected child abuse. Recognizing this leaves children at risk, the Wisconsin Child Abuse Network (WI CAN) sought to understand barriers to mandated reporting and collaboration with child abuse investigators. Objective The purpose of the study was to investigate barriers for professionals in providing and obtaining high-quality medical information in child abuse investigations. Participants and setting Participants included five discipline-specific focus groups: HCPs, child protective services (CPS), law enforcement, lawyers, and judges. All professionals had been directly involved in Wisconsin child abuse cases. Methods This qualitative study consisted of discipline-specific focus groups, directed by open-ended interview questions. Data analysis was completed through the narrative inquiry methodology. Results Barriers to providing and obtaining high-quality medical information in child abuse investigations were both discipline-specific and universal amongst all groups. Discipline-specific barriers included: HCPs’ discomfort with uncertainty; CPS’ perception of disrespect and mistrust by HCPs; law enforcement’s concerns with HCPs’ overstepping professional boundaries; lawyers’ concern of HCPs’ discomfort with court proceedings; and judges’ perception of a lack of understanding between all disciplines. Universal barriers included: value of high-quality medical information in child abuse investigations, burden of time and money; unequal resources between counties; a need for protocols, and a need for interdisciplinary collaboration. Conclusion Findings from this study suggest several ways to address identified barriers. Possible interventions include equalizing resources between urban and rural counties (specifically financial resources and access to child abuse experts); protocolizing reporting and investigations; and, increasing interprofessional education

Toe Brace Designs

In various embodiments, provided are braces for use in supporting the metatarophalangeal joint, reducing or maintaining the intermetatarsal angle, enhancing or maintaining alignment of the hallux, or combinations thereof in a subject having hallux valgus

Toe Joint Replacement Models

In various embodiments, provided are implantable devices for replacing all or a portion of a metatarsophalangeal joint, comprising (i) a metatarsal component comprising a Substan tially convex bearing Surface; or (ii) a phalanx component comprising a Substantially concave bearing Surface; or (iii) both. In various embodiments, also provided are methods of treating hallux Valgus by replacing all or a portion of a meta tarsophalangeal joint with one or more of the provided implantable devices