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

A Moral Bureaucracy: Enforcement of EU Fundamental Values in Central and Eastern Europe

There is growing sentiment that the rise of illiberal democracy in Central and Eastern Europe poses a serious threat to fundamental European values. Within the framework of the European Union (EU) legal system, how do post-socialist member states actually comply with fundamental European values? While there are multiple contradictory theories about the success or failure of assimilation in the region, there is surprisingly little datadriven literature which directly compares post-socialist member state compliance to the rest of the European member states. This paper fills the gap by comparing post-socialist compliance patterns with the rest of the EU, using data on infringement cases opened by the Commission. It finds that post-socialist member states are generally assimilating into pre-existing patterns of European compliance. However, they are demonstrably worse in fundamental European values compliance—and though a legal basis for enforcing these values exists, the EU currently lacks the practical ability to do so

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]

The central amygdala to periaqueductal gray pathway comprises intrinsically distinct neurons differentially affected in a model of inflammatory pain

A major population of neurons in the central nucleus of amygdala (CeA) send projections to the periaqueductal gray (PAG), a key midbrain structure that mediates coping strategies in response to threat or stress. While the CeA‐PAG pathway has proved to be a component of descending anti‐nociceptive circuitry, the functional organization of CeA‐PAG neurons remains unclear. We identified CeA‐PAG neurons in C57BL/6 mice of both sexes using intracranial injection of a fluorescent retrograde tracer into the PAG. In acute brain slices, we investigated the topographical and intrinsic characteristics of retrogradely labelled CeA‐PAG neurons using epifluorescence and whole‐cell electrophysiology. We also measured changes to CeA‐PAG neurons in the complete Freund's adjuvant (CFA) model of inflammatory pain. Neurons in the central lateral (CeL) and central medial (CeM) amygdala project primarily to different regions of the PAG. CeL‐PAG neurons consist of a relatively homogeneous population of intrinsically distinct neurons while CeM‐PAG neurons are intrinsically heterogeneous. Membrane properties of distinct CeM‐PAG subtypes are altered 1 day after induction of the CFA inflammatory pain model. Collectively, our results provide insight into pain‐induced changes to a specific population of CeA neurons that probably play a key role in the integration of noxious input with endogenous analgesia and behavioural coping response

Spared nerve injury differentially alters parabrachial monosynaptic excitatory inputs to molecularly specific neurons in distinct subregions of the central amygdala

Dissecting the organization of circuit pathways involved in pain affect is pivotal for understanding behavior associated with noxious sensory inputs. The central nucleus of the amygdala (CeA) comprises distinct populations of inhibitory GABAergic neurons expressing a wide range of molecular markers. CeA circuits are associated with aversive learning and nociceptive responses. The CeA receives nociceptive signals directly from the parabrachial nucleus (PBn), contributing to the affective and emotional aspects of pain. Although the CeA has emerged as an important node in pain processing, key questions remain regarding the specific targeting of PBn inputs to different CeA subregions and cell types. We used a multifaceted approach involving transgenic reporter mice, viral vector-mediated optogenetics, and brain slice electrophysiology to delineate cell-type–specific functional organization of the PBn–CeA pathway. Whole-cell patch clamp recordings of molecularly defined CeA neurons while optogenetically driving long-range inputs originating from PBn revealed the direct monosynaptic excitatory inputs from PBn neurons to 3 major subdivisions of the CeA: laterocapsular (CeC), lateral (CeL), and medial (CeM). Direct monosynaptic excitatory inputs from PBn targeted both somatostatin-expressing (SOM+) and corticotropin-releasing hormone expressing (CRH+) neurons in the CeA. We find that monosynaptic PBn input is preferentially organized to molecularly specific neurons in distinct subdivisions of the CeA. The spared nerve injury model of neuropathic pain differentially altered PBn monosynaptic excitatory input to CeA neurons based on molecular identity and topographical location within the CeA. These results provide insight into the functional organization of affective pain pathways and how they are altered by chronic pain

Magnetic and vibrational properties of high-entropy alloys

The magnetic properties of high-entropy alloys based on equimolar FeCoCrNi were investigated using vibrating sample magnetometry to determine their usefulness in high-temperature magnetic applications. Nuclear resonant inelastic x-ray scattering measurements were performed to evaluate the vibrational entropy of the ^(57)Fe atoms and to infer chemical order. The configurational and vibrational entropy of alloying are discussed as they apply to these high-entropy alloys

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