Neuroscience
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Dopamine (DA) neurons in the midbrain are crucial for motivational control of behavior. However, recent studies suggest that signals transmitted by DA neurons are heterogeneous. This may reflect a wide range of inputs to DA neurons, but which signals are provided by which brain areas is still unclear. ⋯ Most reward-related signals were positively biased: excitation and inhibition when a better and worse reward was expected, respectively. These PPTg neurons tended to retain the reward value signal until after a reward outcome, representing 'value state'; this was different from DA neurons which show phasic signals representing 'value change'. Our data, together with previous studies, suggest that PPTg neurons send positive reward-related signals mainly to the medial-central SNc where DA neurons encode motivational values, and sensorimotor/arousal signals to the lateral SNc where DA neurons encode motivational salience.
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The C-terminal fragments-25(CTF25) of TDP-43 is a fragment of TAR DNA-binding protein 43kDa (TDP-43), which is involved in RNA metabolism, neurite outgrowth, and neuronal development and stress granules. Not until recently did evidence suggest that CTF25 might play an important role in amyotrophic lateral sclerosis (ALS) pathogenesis. However, mechanical details on CTF25 causing motor neuron degeneration still remain unknown. ⋯ Furthermore, the neurotoxicity of CTF25 of TDP-43 was dependent on proteasome activity. In addition, electron microscopy showed mitochondrial swelling and cristae dilation in cells expressing CTF25 and that CTF25 aggregates were characterized by filamentous bundles and electron dense granular material. In conclusion, the new cellular model mimics classical toxic TDP-43 cellular model and interestingly the toxicity of CTF25 is dependent on the proteasome.
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Sensory experience has a profound effect on neocortical neurons. Passive stimulation of whiskers or sensory deprivation from whiskers can induce long-lasting changes in neuronal responses or modify the receptive field in adult animals. We recorded barrel cortical neurons in urethane-anesthetized rats in layers 2/3 or 5/6 to determine if repetitive stimulation would induce long-lasting response facilitation. ⋯ Inactivation of layer 2/3 also blocked response facilitation in layer 5/6, suggesting that layer 2/3 may be fundamental in this synaptic plasticity processes. Moreover, i.p. injection of eserine augmented the number of layer 2/3 neurons expressing long-lasting response facilitation; this effect was blocked by atropine, suggesting that muscarinic receptor activation favors the induction of the response facilitation. Our data indicate that physiologically repetitive stimulation of a single whisker at the frequency at which rats move their whiskers during exploration of the environment induces long-lasting response facilitation improving sensory processing.
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We employed field potential recordings in extended in vitro brain slices form Sprague-Dawley rats containing the piriform and entorhinal cortices (PC and EC, respectively) to identify the characteristics of epileptiform discharges and concomitant high-frequency oscillations (HFOs, ripples: 80-200Hz, fast ripples: 250-500Hz) during bath application of 4-aminopyridine (4AP, 50μM). Ictal-like discharges occurred in PC and EC either synchronously or independently of each other; synchronous ictal discharges always emerged from a synchronous "fast" interictal background whereas asynchronous ictal discharges were preceded by a "slow" interictal event. ⋯ Finally, antagonizing ionotropic glutamatergic receptors abolished ictal activity in all experiments, increased the duration and rate of occurrence of interictal discharges occurring in PC-EC interconnected slices while it did not influence the slow asynchronous interictal discharges in both areas. Our results identify some novel in vitro interactions between olfactory (PC) and limbic (EC) structures that presumably contribute to in vivo ictogenesis as well.
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Work from the past 40years has unraveled a wealth of information on the cellular and molecular mechanisms underlying synaptic plasticity and their relevance in physiological brain function. At the same time, it has been recognized that a broad range of neurological diseases may be accompanied by severe alterations in synaptic plasticity, i.e., 'maladaptive synaptic plasticity', which could initiate and sustain the remodeling of neuronal networks under pathological conditions. ⋯ This review focuses on recent experimental evidence, which highlights the fundamental role of endoplasmic reticulum-mediated Ca(2+) signals in modulating the duration, direction, extent and type of synaptic plasticity. We discuss the possibility that intracellular Ca(2+) stores may regulate synaptic plasticity and hence behavioral and cognitive functions at the interface between physiology and pathology.