Though the concept of participation of perirhinal cortex and frontal cortex in the processing of ... more Though the concept of participation of perirhinal cortex and frontal cortex in the processing of object memory has long been appreciated, but recently our laboratory extended this to area V2 of visual cortex. We found that activation of area V2 neurons by overexpression of RGS14 protein led to an enhancement of object recognition memory. The memory enhancement was of such extent that it converted the short term memory of 45 minutes into long lasting long-term memory that could be traced even after many months. Here, we have tested the memory enhancer effect of RGS14 in perirhinal cortex (PRh), an area known to be involved in object memory processing, and further explored the relationship of behavioral memory performance with synaptic plasticity within this area. Stimulation of PRh with RGS14 protein produced an equally robust increase in object memory as was observed in area V2. In addition, we found that RGS14-mediated activation of PRh, (i) blocked the depotentiation induced by 1Hz stimulation during 10min; (ii) blocked the LTP induced by 20Hz stimulation while showed no effect at 100Hz stimulation; and (iii) reduced the LTD induced by the application of 20 µM of carbachol, a cholinergic agonist, during 10min, however no effect was observed at a higher concentration (50 µM). Furthermore, we also observed that phosphorylated isoforms of AMPA receptor 1 (iGluR1) were significantly reduced. Thus, our results indicate that iGluR1 reflects the level of synaptic plasticity (LTP and LTD) observed in RGS-animals but lack this correlation in behavioral outcome. This work was supported by projects from MINECO, Junta de Andalucía y NIH.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech
The remedy of memory deficits has been inadequate, as all potential candidates studied thus far h... more The remedy of memory deficits has been inadequate, as all potential candidates studied thus far have shown limited to no effects and a search for an effective strategy is ongoing. Here, we show that an expression of RGS14414 in rat perirhinal cortex (PRh) produced long-lasting object recognition memory (ORM) enhancement and that this effect was mediated through the upregulation of 14-3-3ζ, which caused a boost in BDNF protein levels and increase in pyramidal neuron dendritic arborization and dendritic spine number. A knockdown of the 14-3-3ζ gene in rat or the deletion of the BDNF gene in mice caused complete loss in ORM enhancement and increase in BDNF protein levels and neuronal plasticity, indicating that 14-3-3ζ-BDNF pathway-mediated structural plasticity is an essential step in RGS14414-induced memory enhancement. We further observed that RGS14414 treatment was able to prevent deficits in recognition, spatial, and temporal memory, which are types of memory that are particularly...
Memory deficits affect a large proportion of the human population and are associated with aging a... more Memory deficits affect a large proportion of the human population and are associated with aging and many neurologic, neurodegenerative, and psychiatric diseases. Treatment of this mental disorder has been disappointing because all potential candidates studied thus far have failed to produce consistent effects across various types of memory and have shown limited to no effects on memory deficits. Here, we show that the promotion of neuronal arborization through the expression of the regulator of G-protein signaling 14 of 414 amino acids (RGS14 414) not only induced robust enhancement of multiple types of memory but was also sufficient for the recovery of recognition, spatial, and temporal memory, which are kinds of episodic memory that are primarily affected in patients or individuals with memory dysfunction. We observed that a surge in neuronal arborization was mediated by up-regulation of brain-derived neurotrophic factor (BDNF) signaling and that the deletion of BDNF abrogated both neuronal arborization activation and memory enhancement. The activation of BDNF-dependent neuronal arborization generated almost 2-fold increases in synapse numbers in dendrites of pyramidal neurons and in neurites of nonpyramidal neurons. This increase in synaptic connections might have evoked reorganization within neuronal circuits and eventually supported an increase in the activity of such circuits. Thus, in addition to showing the potential of RGS14 414 for rescuing memory deficits, our results suggest that a boost in circuit activity could facilitate memory enhancement and the reversal of memory deficits.
Though the concept of participation of perirhinal cortex and frontal cortex in the processing of ... more Though the concept of participation of perirhinal cortex and frontal cortex in the processing of object memory has long been appreciated, but recently our laboratory extended this to area V2 of visual cortex. We found that activation of area V2 neurons by overexpression of RGS14 protein led to an enhancement of object recognition memory. The memory enhancement was of such extent that it converted the short term memory of 45 minutes into long lasting long-term memory that could be traced even after many months. Here, we have tested the memory enhancer effect of RGS14 in perirhinal cortex (PRh), an area known to be involved in object memory processing, and further explored the relationship of behavioral memory performance with synaptic plasticity within this area. Stimulation of PRh with RGS14 protein produced an equally robust increase in object memory as was observed in area V2. In addition, we found that RGS14-mediated activation of PRh, (i) blocked the depotentiation induced by 1Hz stimulation during 10min; (ii) blocked the LTP induced by 20Hz stimulation while showed no effect at 100Hz stimulation; and (iii) reduced the LTD induced by the application of 20 µM of carbachol, a cholinergic agonist, during 10min, however no effect was observed at a higher concentration (50 µM). Furthermore, we also observed that phosphorylated isoforms of AMPA receptor 1 (iGluR1) were significantly reduced. Thus, our results indicate that iGluR1 reflects the level of synaptic plasticity (LTP and LTD) observed in RGS-animals but lack this correlation in behavioral outcome. This work was supported by projects from MINECO, Junta de Andalucía y NIH.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech
The remedy of memory deficits has been inadequate, as all potential candidates studied thus far h... more The remedy of memory deficits has been inadequate, as all potential candidates studied thus far have shown limited to no effects and a search for an effective strategy is ongoing. Here, we show that an expression of RGS14414 in rat perirhinal cortex (PRh) produced long-lasting object recognition memory (ORM) enhancement and that this effect was mediated through the upregulation of 14-3-3ζ, which caused a boost in BDNF protein levels and increase in pyramidal neuron dendritic arborization and dendritic spine number. A knockdown of the 14-3-3ζ gene in rat or the deletion of the BDNF gene in mice caused complete loss in ORM enhancement and increase in BDNF protein levels and neuronal plasticity, indicating that 14-3-3ζ-BDNF pathway-mediated structural plasticity is an essential step in RGS14414-induced memory enhancement. We further observed that RGS14414 treatment was able to prevent deficits in recognition, spatial, and temporal memory, which are types of memory that are particularly...
Memory deficits affect a large proportion of the human population and are associated with aging a... more Memory deficits affect a large proportion of the human population and are associated with aging and many neurologic, neurodegenerative, and psychiatric diseases. Treatment of this mental disorder has been disappointing because all potential candidates studied thus far have failed to produce consistent effects across various types of memory and have shown limited to no effects on memory deficits. Here, we show that the promotion of neuronal arborization through the expression of the regulator of G-protein signaling 14 of 414 amino acids (RGS14 414) not only induced robust enhancement of multiple types of memory but was also sufficient for the recovery of recognition, spatial, and temporal memory, which are kinds of episodic memory that are primarily affected in patients or individuals with memory dysfunction. We observed that a surge in neuronal arborization was mediated by up-regulation of brain-derived neurotrophic factor (BDNF) signaling and that the deletion of BDNF abrogated both neuronal arborization activation and memory enhancement. The activation of BDNF-dependent neuronal arborization generated almost 2-fold increases in synapse numbers in dendrites of pyramidal neurons and in neurites of nonpyramidal neurons. This increase in synaptic connections might have evoked reorganization within neuronal circuits and eventually supported an increase in the activity of such circuits. Thus, in addition to showing the potential of RGS14 414 for rescuing memory deficits, our results suggest that a boost in circuit activity could facilitate memory enhancement and the reversal of memory deficits.
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Papers by Gloria Delgado