Neuroscience
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Studies in rodent models of acute and chronic neurodegenerative disorders have uncovered that glutamate-induced excitotoxic cell death is mediated primarily by extrasynaptic N-methyl-d-aspartate receptors (NMDARs). Rodent neurons can also build up in an activity-dependent manner a protective shield against excitotoxicity. This form of acquired neuroprotection is induced by preconditioning with low doses of NMDA or by activation of synaptic NMDARs triggered by bursts of action potentials. ⋯ Moreover, we found that conditions of enhanced synaptic activity increased survival of human iPSC-derived neurons if applied as pre-treatment before toxic NMDA application. These results revealed that both toxic and protective actions of NMDARs are preserved in human neurons. The experimental platform described in this study may prove useful for the validation of neuroprotective gene products and drugs in human neurons.
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In recent years there has been an increase in the development of new synthetic drugs, among which the "bath salt" 3,4-methylenedioxypyrovalerone (MDPV), a psychostimulant with a mechanism of action similar to those of cocaine and amphetamine, stands out. Drugs of abuse have been consistently shown to affect memory function in male rodents. We have recently shown that amphetamine and MDPV induce generalization of fear memory in an inhibitory avoidance discrimination task in male rats. ⋯ On day 1 of the experimental protocol, all rats were exposed to a safe context and, the day after, to a slightly different chamber where they received an unsignaled footshock. Twenty-four and forty-eight hours later, freezing behavior and emission of 22 kHz-ultrasonic vocalizations (USVs) were measured in the two different contexts to assess fear memory retention and generalization. Our results indicate that MDPV treatment altered freezing in both sexes, USVs were affected by amphetamine in males while by MDPV in females.
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The electrophysiological properties of undifferentiated SH-SY5Y cells were examined during cultures prolonged even to 20 days by measuring the passive and active membrane properties at 5 days interval, as well as the spontaneous spiking activity. The results showed that culturing this cell for long time affected not only membrane shape but also their electrophysiological properties. ⋯ These modifications would synergically contribute to the bioelectrical conversion of these cells and could be part of a more complex machinery with which the tumoral cell would regulate its survival advantage and resilience. Understanding these processes could add a new clue to the exploitation of this preclinical human neuronal model.
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Fear memories allow animals to recognize and adequately respond to dangerous situations. The prelimbic cortex (PrL) is a crucial node in the circuitry that encodes contextual fear memory, and its activity is central for fear memory expression over time. However, while PrL has been implicated in contextual fear memory storage, the molecular mechanisms underlying its maintenance remain unclear. ⋯ Also, PKMζ inhibition in the PrL does not impair the maintenance of recent contextual fear memory. However, we found that inhibition of prelimbic PKMζ at a remote time point disrupts contextual fear memory maintenance, and that blocking GluA2-dependent removal of AMPARs prevents this impairment. Our results confirm the central role of PrL in fear memory and identify PKMζ-induced inhibition of GluA2-containing AMPAR endocytosis as a key mechanism governing remote contextual fear memory maintenance.