Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents

Shetty, Mahabalesh; Sharma, Mahima; Hui, Neo Sin; Dasgupta, Ananya; Gopinadhan, Suma; Sajikumar, Sreedharan

doi:10.3791/53008-v

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…Transverse hippocampal slices were prepared as described previously (Shetty et al ., 2015). Briefly, animals were sacrificed by cervical dislocation followed by decapitation, and the brain was quickly removed and placed in ice-cold aCSF (124 mM NaCl, 4.4 mM KCl, 2.5 mM CaCl 2 , 1.3 mM MgCl 2 , 1 mM NaH 2 PO 4 , 10 mM glucose and buffered with 26.2 mM NaHCO 3 ) bubbled constantly with carbogen and the hippocampus was dissected out with a sickle scaler.…”

Section: Methodsmentioning

confidence: 99%

Differential effects of PDE4A5 on cAMP-dependent forms of long-term potentiation

Tadinada,

Walsh,

Mukherjee

et al. 2024

Preprint

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cAMP signaling is critical for memory consolidation and certain of forms long-term potentiation (LTP). Phosphodiesterases (PDEs), enzymes that degrade the second messenger cAMP and cGMP, are highly conserved during evolution and represent a unique set of drug targets, given the involvement of these enzymes in several pathophysiological states including brain disorders. The PDE4 family of cAMP selective PDEs, exert regulatory roles in memory and synaptic plasticity, but the specific roles of distinct PDE4 isoforms in these processes are poorly understood. Building on our previous work demonstrating that spatial and contextual memory deficits were caused by expressing selectively the long isoform of the PDE4A subfamily, PDE4A5, in hippocampal excitatory neurons, we now investigate the effects of PDE4A isoforms on different cAMP-dependent forms of LTP. We find that PDE4A5 impairs long-lasting LTP induced by theta burst stimulation (TBS) while sparing long-lasting LTP induced by spaced 4-train stimulation (4X100Hz). This effect requires the unique N-terminus of PDE4A5 and is specific to this long isoform. Targeted overexpression of PDE4A5 in area CA1 is sufficient to impair TBS-LTP, suggesting that cAMP levels in the postsynaptic neuron are critical for TBS-LTP. Our results shed light on the inherent differences among the PDE4A subfamily isoforms, emphasizing the importance of the long isoforms, which have a unique N-terminal region. Advancing our understanding of the function of specific PDE isoforms will pave the way for developing isoform-selective approaches to treat the cognitive deficits that are debilitating aspects of psychiatric, neurodevelopmental, and neurodegenerative disorders.

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Section: Methodsmentioning

confidence: 99%

Differential effects of PDE4A5 on cAMP-dependent forms of long-term potentiation

Tadinada,

Walsh,

Mukherjee

et al. 2024

Preprint

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“…Immediately prior to application, they were both diluted in ACSF to a final concentration of 1 μM and bubbled with carbogen. For further details regarding the protocol, please refer to 45 …”

Section: Methodsmentioning

confidence: 99%

Aging inverts the effects of p75^NTR‐modulated mTOR manipulation on hippocampal neuron synaptic plasticity in male mice

et al. 2023

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Age-induced impairments in learning and memory are in part caused by changes to hippocampal synaptic plasticity during aging. The p75 neurotrophin receptor (p75 NTR ) and mechanistic target of rapamycin (mTOR) are implicated in synaptic plasticity processes. mTOR is also well known for its involvement in aging.Recently, p75 NTR and mTOR were shown to be mechanistically linked, and that p75 NTR mediates age-induced impairment of hippocampal synaptic plasticity. Yet the consequences of p75 NTR -mTOR interaction on hippocampal synaptic plasticity, and the role of mTOR in age-induced cognitive decline, are unclear. In this study, we utilize field electrophysiology to study the effects of mTOR inhibition and activation on long-term potentiation (LTP) in male young and aged wild-type (WT) mice. We then repeated the experiments on p75 NTR knockout mice. The results demonstrate that mTOR inhibition blocks late-LTP in young WT mice but rescues age-related late-LTP impairment in aged WT mice. mTOR activation suppresses late-LTP in aged WT mice while lacking observable effects on young WT mice. These effects were not observed in p75 NTR knockout mice. These results demonstrate that the role of mTOR in hippocampal synaptic plasticity is distinct between young and aged mice. Such effects could be explained by differing sensitivity of young and aged hippocampal neurons to changes in protein synthesis or autophagic activity levels. Additionally, elevated mTOR in the aged hippocampus could cause excessive mTOR signaling, which is worsened by activation and alleviated by inhibition. Further research on mTOR and p75 NTR may prove useful

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“…Transverse slices (400 μm) from the right and left hippocampus were prepared by using a manual tissue chopper, transferred onto a nylon net in an interface chamber (Scientific Systems Design), and incubated at 32°C for 3 h. An aCSF flow rate of 1 mL/min and carbogen consumption of 16 L/h were maintained throughout the experiment. The whole process was carried out within 5 min (Shetty et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

Alteration of hippocampal CA2 plasticity and social memory in adult rats impacted by juvenile stress

2023

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The hippocampal CA2 region has received greater attention in recent years due to its fundamental role in social memory and hippocampus-dependent memory processing.Unlike entorhinal cortical inputs, the Schaffer collateral inputs to CA2 do not support activity-dependent long-term potentiation (LTP), which serves as the basis for longterm memories. This LTP-resistant zone also expresses genes that restrict plasticity.With the aim of exploring social interaction and sociability in rats that were subjected to juvenile stress, we addressed questions about how the neural circuitry is altered and its effects on social behavior. Although there was induction of LTP in both Schaffer collateral and entorhinal cortical pathways in juvenile-stressed rats, LTP declined in both pathways after 2-3 h. Moreover, exogenous bath application of substance P, a neuropeptide that resulted in slow onset long-lasting potentiation in control animals while it failed to induce LTP in juvenile-stressed rats. Our study reveals that juvenilestressed rats show behavioral and cellular abnormalities with a long-lasting impact in adulthood.

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Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents

Cited by 8 publications

References 17 publications

Differential effects of PDE4A5 on cAMP-dependent forms of long-term potentiation

Differential effects of PDE4A5 on cAMP-dependent forms of long-term potentiation

Aging inverts the effects of p75^NTR‐modulated mTOR manipulation on hippocampal neuron synaptic plasticity in male mice

Alteration of hippocampal CA2 plasticity and social memory in adult rats impacted by juvenile stress

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Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents

Cited by 8 publications

References 17 publications

Differential effects of PDE4A5 on cAMP-dependent forms of long-term potentiation

Differential effects of PDE4A5 on cAMP-dependent forms of long-term potentiation

Aging inverts the effects of p75NTR‐modulated mTOR manipulation on hippocampal neuron synaptic plasticity in male mice

Alteration of hippocampal CA2 plasticity and social memory in adult rats impacted by juvenile stress

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Aging inverts the effects of p75^NTR‐modulated mTOR manipulation on hippocampal neuron synaptic plasticity in male mice