7,215 research outputs found

    Fear Conditioning Potentiates Synaptic Transmission onto Long-Range Projection Neurons in the Lateral Subdivision of Central Amygdala

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    Recent studies indicate that the lateral subdivision of the central amygdala (CeL) is essential for fear learning. Specifically, fear conditioning induces cell-type-specific synaptic plasticity in CeL neurons that is required for the storage of fear memories. The CeL also controls fear expression by gating the activity of the medial subdivision of the central amygdala (CeM), the canonical amygdala output to areas that mediate defensive responses. In addition to the connection with CeM, the CeL sends long-range projections to innervate extra-amygdala areas. However, the long-range projection CeL neurons have not been well characterized, and their role in fear regulation is unknown. Here we show in mice that a subset of CeL neurons directly project to the midbrain periaqueductal gray (PAG) and the paraventricular nucleus of the thalamus, two brain areas implicated in defensive behavior. These long-range projection CeL neurons are predominantly somatostatin-positive (SOM(+)) neurons, which can directly inhibit PAG neurons, and some of which innervate both the PAG and paraventricular nucleus of the thalamus. Notably, fear conditioning potentiates excitatory synaptic transmission onto these long-range projection CeL neurons. Thus, our study identifies a subpopulation of SOM(+) CeL neurons that may contribute to fear learning and regulate fear expression independent of CeM

    Parvalbumin interneuron dysfunction in a thalamo-prefrontal cortical circuit in Disc1 locus impairment mice

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    Altered cortical excitation-inhibition (E-I) balance resulting from abnormal parvalbumin interneuron (PV IN) function is a proposed pathophysiological mechanism of schizophrenia (SZ) and other major psychiatric disorders. Preclinical studies have indicated that disrupted-in-schizophrenia-1 (DISC1) is a useful molecular lead to address the biology of prefrontal cortex dependent cognition and PV IN function. To date, prefrontal cortical inhibitory circuit function has not been investigated in depth in Disc1 locus impairment (LI) mouse models. Therefore, we used a Disc1 LI mouse model to investigate E-I balance in medial prefrontal cortical (mPFC) circuits. We found that inhibition onto layer 3 excitatory pyramidal neurons in the mPFC was significantly reduced in Disc1 LI mice. This reduced inhibition was accompanied by decreased GABA release from local PV, but not somatostatin (SOM) interneurons, and by impaired feedforward inhibition in the mediodorsal thalamus (MD) to mPFC circuit. Our mechanistic findings of abnormal PV IN function in a Disc1 LI model provide insight into biology that may be relevant to neuropsychiatric disorders including schizophrenia.SIGNIFICANCE STATEMENT A popular theory suggests that dysregulation of fast-spiking parvalbumin interneurons (PV INs) and elevated excitation-inhibition (E-I) balance contribute to the pathophysiology of various psychiatric disorders. Previous studies suggest that genetic perturbations of the disrupted-in-schizophrenia-1 (Disc1) gene affect prefrontal cortex-dependent cognition and PV IN function, but synaptic and circuit physiology data are lacking. Here, we provide evidence that the presynaptic function of PV INs in the medial prefrontal cortex is altered in Disc1 LI mice and that E-I balance is elevated within a thalamofrontal circuit known to be important for cognition. These findings may contribute to our understanding of the biology that gives rise to cognitive symptoms in a range of neuropsychiatric disorders

    A New Scintillator Tile/Fiber Preshower Detector for the CDF Central Calorimeter

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    A detector designed to measure early particle showers has been installed in front of the central CDF calorimeter at the Tevatron. This new preshower detector is based on scintillator tiles coupled to wavelength-shifting fibers read out by multi-anode photomultipliers and has a total of 3,072 readout channels. The replacement of the old gas detector was required due to an expected increase in instantaneous luminosity of the Tevatron collider in the next few years. Calorimeter coverage, jet energy resolution, and electron and photon identification are among the expected improvements. The final detector design, together with the R&D studies that led to the choice of scintillator and fiber, mechanical assembly, and quality control are presented. The detector was installed in the fall 2004 Tevatron shutdown and started collecting colliding beam data by the end of the same year. First measurements indicate a light yield of 12 photoelectrons/MIP, a more than two-fold increase over the design goals.Comment: 5 pages, 10 figures (changes are minor; this is the final version published in IEEE-Trans.Nucl.Sci.

    Design and construction of new central and forward muon counters for CDF II

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    New scintillation counters have been designed and constructed for the CDF upgrade in order to complete the muon coverage of the central CDF detector, and to extend this coverage to larger pseudorapidity. A novel light collection technique using wavelength shifting fibers, together with high quality polystyrene-based scintillator resulted in compact counters with good and stable light collection efficiency over lengths extending up to 320 cm. Their design and construction is described and results of their initial performance are reported.Comment: 20 pages, 15 figure

    Cyclic nucleotide signalling in malaria parasites.

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    The cyclic nucleotides 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP) are intracellular messengers found in most animal cell types. They usually mediate an extracellular stimulus to drive a change in cell function through activation of their respective cyclic nucleotide-dependent protein kinases, PKA and PKG. The enzymatic components of the malaria parasite cyclic nucleotide signalling pathways have been identified, and the genetic and biochemical studies of these enzymes carried out to date are reviewed herein. What has become very clear is that cyclic nucleotides play vital roles in controlling every stage of the complex malaria parasite life cycle. Our understanding of the involvement of cyclic nucleotide signalling in orchestrating the complex biology of malaria parasites is still in its infancy, but the recent advances in our genetic tools and the increasing interest in signalling will deliver more rapid progress in the coming years
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