scholarly journals Tonic activation of VPAC1 receptors by VIP modulates theta-burst induced LTP in the hippocampus: transduction pathways and GABAergic mechanisms.

2021 ◽  
Author(s):  
Nadia Rodrigues ◽  
Ana Caulino-Rocha ◽  
Joaquim Ribeiro ◽  
Diana Cunha-Reis
Keyword(s):  
Young Adult ◽  
Potassium Channels ◽  
Pyramidal Cell ◽  
Wistar Rats ◽  
Hippocampal Slices ◽  
Electrophysiological Recordings ◽  
Hippocampal Ca1 ◽  
Vpac Receptors ◽  
Ca1 Area ◽  
Theta Burst

Background and purpose Vasoactive intestinal peptide (VIP), acting on both VPAC and VPAC receptors, is a key modulator of hippocampal synaptic transmission, pyramidal cell excitability and synaptic plasticity phenomena, like long-term depression (LTD), partly through modulation GABAergic disinhibitory circuits. VIP effects on LTP and the involvement of disinhibition were scarcely investigated. Experimental approach The influence of endogenous VIP on CA1 LTP induced by TBS was evaluated in the CA1 area of hippocampal slices using field-excitatory electrophysiological recordings from young-adult Wistar rats using selective VPAC and VPAC antagonists. Phosphorylation of GluA1 AMPA receptor subunits and Kv4.2 potassium channels was evaluated in hippocampal membranes obtained from such slices by Western blot. Key results Here we show that VIP, acting on VPAC (but not VPAC) receptors, is an endogenous inhibitor of hippocampal LTP induced by theta-burst stimulation (TBS) in the CA1 area of the hippocampus of young adult Wistar rats. This effect is dependent on GABAergic transmission and relies on the integrity of NMDA and CaMKII-dependent LTP expression mechanisms but not on PKA and PKC activity. Furthermore, it regulates the expression and Serphosphorylation of Kv4.2 potassium channels responsible for the A-current while inhibiting phosphorylation of Kv4.2 on Thr. Conclusions and implications Altogether this suggests that endogenous VIP controls the expression of hippocampal CA1 LTP by regulating disinhibition through activation of VPAC receptors in interneurons. This may impact the expression and phosphorylation of Kv4.2 K channels at hippocampal pyramidal cell dendrites.

scholarly journals PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pojeong Park ◽  
John Georgiou ◽  
Thomas M. Sanderson ◽  
Kwang-Hee Ko ◽  
Heather Kang ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Single Channel ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Theta Burst Stimulation ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Necessary And Sufficient ◽  
Theta Burst

AbstractLong-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTPγ), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTPN whilst PKA is additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.

scholarly journals Oxytocin protects neurons from hypoxic-ischemic brain injury by enhancing inhibitory neurotransmission in neonatal rats

2021 ◽  
Vol 20 (9) ◽  
pp. 1909-1914
Author(s):  
Linhua Xiang ◽  
Rong Wu ◽  
Kangling Liu ◽  
Jing Wang
Keyword(s):  
Protective Effect ◽  
Hippocampal Slices ◽  
Time Lapse ◽  
Oxytocin Receptor ◽  
Neonatal Rats ◽  
Model Group ◽  
Ischemic Brain ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area

Purpose: To study the protective effect of oxytocin on hypoxic-ischemic brain neuron injury in neonatal rats, and the mechanism of action involved.Methods: Hippocampal slices from neonatal SD rats were cultured in oxygen/glucose-deprived (OGD) solution, leading to establishment of hypoxic-ischemic model of hippocampal slices in vitro. The slices were assigned to 3 groups: control (ACSF solution), model (OGD solution), and oxytocin (OGD solution + 1 μM oxytocin). The effect of oxytocin on vertebral neurons in hippocampal CA1 region of HIBD rats was determined using TOPRO-3 staining, while the effects of oxytocin on hypoxic depolarization (AD) and inhibitory postsynaptic currents (iPSCs) were measured by cell patch clamp technique.Results: The fluorescence intensity of vertebral lamina in hippocampal CA1 area of model group was significantly higher than that of control group, while the corresponding value for oxytocin group was significantly lower than that of model group (p < 0.05). The time lapse before occurrence of AD in hippocampal CA1 area was significantly longer in oxytocin group than in model group, while the time lapse before neuronal AD in oxytocin receptor antagonist group was lower than that in oxytocin group. The frequency and amplitude of iPSCs in oxytocin group were markedly higher than the corresponding control values.Conclusion: Oxytocin exerts protective effect against hypoxic-ischemic brain neuronal damage in neonatal rats by regulating the activation of oxytocin receptor and GABA receptor, and inhibiting nerve transmission. These findings may be of benefit in the development of a suitable therapy for HIBD.

Prenatal Dietary Choline Supplementation Decreases the Threshold for Induction of Long-Term Potentiation in Young Adult Rats

1998 ◽  
Vol 79 (4) ◽  
pp. 1790-1796 ◽  
Author(s):  
Gowri K. Pyapali ◽  
Dennis A. Turner ◽  
Christina L. Williams ◽  
Warren H. Meck ◽  
H. Scott Swartzwelder
Keyword(s):  
Young Adult ◽  
Hippocampal Slices ◽  
Threshold Level ◽  
Long Term Potentiation ◽  
Adult Rats ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
Dietary Choline ◽  
Theta Burst

Pyapali, Gowri K., Dennis A. Turner, Christina L. Williams, Warren H. Meck, and H. Scott Swartzwelder. Prenatal dietary choline supplementation decreases the threshold for induction of long-term potentiation in young adult rats. J. Neurophysiol. 79: 1790–1796, 1998. Choline supplementation during gestation in rats leads to augmentation of spatial memory in adulthood. We hypothesized that prenatal (E12–E17) choline supplementation in the rat would lead to an enhancement of hippocampal synaptic plasticity as assessed by long-term potentiation (LTP) at 3–4 mo of age. LTP was assessed blindly in area CA1 of hippocampal slices with first suprathreshold (above threshold for LTP generation in control slices) theta-burst stimulus trains. The magnitude of potentiation after these stimuli was not different between slices from control and prenatally choline supplemented animals. Next, threshold (reliably leading to LTP generation in control slices) or subthreshold theta-burst stimulus trains were applied to slices from control, prenatally choline-supplemented, and prenatally choline-deprived rats. Threshold level stimulus trains induced LTP in slices from both the control and choline-supplemented rats but not in those from the choline-deficient rats. Subthreshold stimulus trains led to LTP induction in slices from prenatally choline-supplemented rats only. These observations indicate that prenatal dietary manipulation of the amino acid, choline, leads to subsequent significant alterations of LTP induction threshold in adult animals.

scholarly journals PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus

2020 ◽  
Author(s):  
Pojeong Park ◽  
John Georgiou ◽  
Thomas M. Sanderson ◽  
Kwang-Hee Ko ◽  
Heather Kang ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Single Channel ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Theta Burst Stimulation ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Necessary And Sufficient ◽  
Theta Burst

ABSTRACTLong-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involved purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA was activated, resulted in LTP that was associated with a transient increase in γ (LTPγ). This γ increase was due to the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII was necessary and sufficient for LTPN whilst PKA was additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.

scholarly journals Learning differentially shapes prefrontal and hippocampal activity during classical conditioning

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jan L Klee ◽  
Bryan C Souza ◽  
Francesco P Battaglia
Keyword(s):  
Classical Conditioning ◽  
Single Cell ◽  
Activity Patterns ◽  
Population Level ◽  
Electrophysiological Recordings ◽  
Hippocampal Activity ◽  
Hippocampal Ca1 ◽  
Persistent Firing ◽  
Ca1 Area ◽  
Assembly Activity

The ability to use sensory cues to inform goal directed actions is a critical component of behavior. To study how sounds guide anticipatory licking during classical conditioning, we employed high-density electrophysiological recordings from the hippocampal CA1 area and the prefrontal cortex (PFC) in mice. CA1 and PFC neurons undergo distinct learning dependent changes at the single cell level and maintain representations of cue identity at the population level. In addition, reactivation of task-related neuronal assemblies during hippocampal awake Sharp-Wave Ripples (aSWR) changed within individual sessions in CA1 and over the course of multiple sessions in PFC. Despite both areas being highly engaged and synchronized during the task, we found no evidence for coordinated single cell or assembly activity during conditioning trials or aSWR. Taken together, our findings support the notion that persistent firing and reactivation of task-related neural activity patterns in CA1 and PFC support learning during classical conditioning.

scholarly journals Cellular and molecular mechanisms involved in LTP induced by mild theta-burst stimulation in hippocampal slices from young male rats: from weaning to adulthood

2021 ◽  
Author(s):  
NC Rodrigues ◽  
A Silva-Cruz ◽  
A Caulino-Rocha ◽  
A Bento-Oliveira ◽  
JA Ribeiro ◽  
...  
Keyword(s):  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Male Rats ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Cellular Models ◽  
Erk Mapk ◽  
Ca1 Area ◽  
Theta Burst

AbstractLong-term potentiation (LTP) is a highly studied phenomenon yet the essential vs. modulatory transduction and GABAergic pathways involved in LTP elicited by theta-burst stimulation (TBS) in the CA1 area of the hippocampus are still unclear, due to the use of different TBS intensities and patterns or of different rodent/cellular models. We now characterized the essential transduction and GABAergic pathways in mild TBS-induced LTP in the CA1 area of the rat hippocampus. LTP induced by TBS (5×4) (5 bursts of 4 pulses delivered at 100Hz) lasted for up to 3h and was increasingly greater from weaning to adulthood. Stronger TBS patterns - TBS (15×4) or three TBS (15×4) separated by 6 min induced nearly maximal LTP not being the best choice to study the value of LTP-enhancing drugs. LTP induced by TBS (5×4) was fully dependent on NMDA receptor and CaMKII activity but independent on PKA or PKC activity. In addition, it was partially dependent on GABAB receptor activation and was potentiated by GABAA receptor blockade and less by GAT-1 transporter blockade. AMPA GluA1 phosphorylation on Ser831 (CaMKII target) but not GluA1 Ser845 (PKA target) was essential for LTP expression. The phosphorylation of the Kv4.2 channel was observed at Ser438 (targeted by CaMKII) but not at Thr602 or Thr607 (ERK/MAPK pathway). This suggests that cellular kinases like PKA, PKC or kinases of the ERK/MAPK family although important modulators of TBS (5×4)-induced LTP are not essential for its expression in the CA1 area of the hippocampus.

Extracellular alkaline shifts in rat hippocampal slice are mediated by NMDA and non-NMDA receptors

1992 ◽  
Vol 68 (1) ◽  
pp. 342-344 ◽  
Author(s):  
J. C. Chen ◽  
M. Chesler
Keyword(s):  
Hippocampal Slice ◽  
Hippocampal Slices ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Alkaline Shift ◽  
Hippocampal Ca1 ◽  
Antidromic Stimulation ◽  
Nmda Glutamate Receptors ◽  
Cell Firing ◽  
Ca1 Area

1. The pharmacology of synaptically evoked extracellular alkaline shifts was studied in the CA1 area of rat hippocampal slices. 2. Stimulus-evoked alkalinizations were unaffected by 2-amino-5-phosphonovalerate (APV) (20 microM). 3. 6-Cyano-7-nitro-nitroquinoxaline-2,3-dione (CNQX) (10 microM) inhibited the alkalinizations. In the continued presence of CNQX, an APV-sensitive, picrotoxin-insensitive, alkaline shift was elicited in low Mg2+ media. 4. Antidromic stimulation produced small alkaline shifts in comparison with orthodromic activation. 5. Our results demonstrate that in the hippocampal CA1 region, synaptically evoked alkalinizations can arise through both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. These responses cannot be explained by cell firing per se.

scholarly journals Interplay between 5-HT4 Receptors and GABAergic System within CA1 Hippocampal Synaptic Plasticity

2020 ◽  
Vol 31 (1) ◽  
pp. 694-701
Author(s):  
Pierre Lecouflet ◽  
Candice M Roux ◽  
Brigitte Potier ◽  
Marianne Leger ◽  
Elie Brunet ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Serotonin Receptor ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Gabaergic Neurotransmission ◽  
Hippocampal Synaptic Plasticity ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca1 Area ◽  
Ca1 Area ◽  
Theta Burst

Abstract The type 4 serotonin receptor (5-HT4R) is highly involved in cognitive processes such as learning and memory. Behavioral studies have shown a beneficial effect of its activation and conversely reported memory impairments by its blockade. However, how modulation of 5HT4R enables modifications of hippocampal synaptic plasticity remains elusive. To shed light on the mechanisms at work, we investigated the effects of the 5-HT4R agonist RS67333 on long-term potentiation (LTP) within the hippocampal CA1 area. Although high-frequency stimulation-induced LTP remained unaffected by RS67333, the magnitude of LTP induced by theta-burst stimulation was significantly decreased. This effect was blocked by the selective 5-HT4R antagonist RS39604. Further, 5-HT4R-induced decrease in LTP magnitude was fully abolished in the presence of bicuculline, a GABAAR antagonist; hence, demonstrating involvement of GABA neurotransmission. In addition, we showed that the application of a GABABR antagonist, CGP55845, mimicked the effect of 5-HT4R activation, whereas concurrent application of CGP55845 and RS67333 did not elicit an additive inhibition effect on LTP. To conclude, through investigation of theta burst induced functional plasticity, we demonstrated an interplay between 5-HT4R activation and GABAergic neurotransmission within the hippocampal CA1 area.

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