scholarly journals IGF-1 facilitates extinction of conditioned fear

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Laura E Maglio ◽  
José A Noriega-Prieto ◽  
Irene B Maroto ◽  
Jesús Martin-Cortecero ◽  
Antonio Muñoz-Callejas ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Conditioned Fear ◽  
Long Term Potentiation ◽  
Fear Extinction ◽  
Neuronal Firing ◽  
Term Potentiation ◽  
Extinction Memory

Insulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, spatial learning and anxiety-like behavioral processes. While IGF-1 regulates neuronal firing and synaptic transmission in many areas of the central nervous system, its signaling and consequences on excitability, synaptic plasticity, and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the rat infralimbic cortex. Besides, IGF-1 mediates a presynaptic long-term depression of both inhibitory and excitatory synaptic transmission in these neurons. The net effect of this IGF-1 mediated synaptic plasticity is a long-term potentiation of the postsynaptic potentials. Moreover, we demonstrate that IGF-1 favors the fear extinction memory. These results show novel functional consequences of IGF-1 signaling, revealing IGF-1 as a key element in the control of the fear extinction memory.

scholarly journals IGF-1 facilitates extinction of conditioned fear

2020 ◽  
Author(s):  
José A. Noriega-Prieto ◽  
Laura E. Maglio ◽  
Irene B. Maroto ◽  
Jesús Martin-Cortecero ◽  
Antonio Muñoz-Callejas ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Plasticity ◽  
Animal Behavior ◽  
Pyramidal Neurons ◽  
Conditioned Fear ◽  
Fear Extinction ◽  
Neuronal Firing ◽  
Infralimbic Cortex ◽  
Regulatory Processes ◽  
Extinction Memory

SUMMARYInsulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, degenerative diseases, spatial learning, and anxiety-like behavioral processes. While IGF-1 regulates neuronal activity in many areas of the brain, its effect on synaptic plasticity and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the infralimbic cortex. Besides, IGF-1 mediates a long-term depression of both inhibitory and excitatory synaptic transmission that results in a longterm potentiation of the postsynaptic potentials. We demonstrate that these synaptic and intrinsic regulatory processes mediated by IGF-1 favor the fear extinction memory. These results show novel functional consequences of IGF-1 signaling on animal behavior tasks dependent on the prefrontal cortex, revealing IGF-1 as a key element in the control of the fear extinction memory.Impact StatementIGF-1 modulates the neuronal firing and synaptic plasticity in infralimbic cortex, favoring the extinction memory

scholarly journals Oxytocin increases inhibitory synaptic transmission and blocks development of long-term potentiation in the lateral amygdala

2020 ◽  
Vol 123 (2) ◽  
pp. 587-599 ◽  
Author(s):  
J. W. Crane ◽  
N. M. Holmes ◽  
J. Fam ◽  
R. F. Westbrook ◽  
A. J. Delaney
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Lateral Amygdala ◽  
Term Potentiation ◽  
Cortical Inputs

Oxytocin (OT) is a neuroactive peptide that influences the processing of fearful stimuli in the amygdala. In the central nucleus of the amygdala, the activation of OT receptors alters neural activity and ultimately suppresses the behavioral response to a fear conditioned stimulus. Receptors for OT are also found in the lateral amygdala (LA), and infusion of OT into the basolateral amygdala complex affects the formation and consolidation of fear memories. Yet, how OT receptor activation alters neurons and neural networks in the LA is unknown. In this study we used whole cell electrophysiological recordings to determine how OT-receptor activation changes synaptic transmission and synaptic plasticity in the LA of Sprague-Dawley rats. Our results demonstrate that OT-receptor activation results in a 200% increase in spontaneous inhibitory transmission in the LA that leads to the activation of presynaptic GABAB receptors. The activation of these receptors inhibits excitatory transmission in the LA, blocking long-term potentiation of cortical inputs onto LA neurons. Hence, this study provides the first demonstration that OT influences synaptic transmission and plasticity in the LA, revealing a mechanism that could explain how OT regulates the formation and consolidation of conditioned fear memories in the amygdala. NEW & NOTEWORTHY This study investigates modulation of synaptic transmission by oxytocin (OT) in the lateral amygdala (LA). We demonstrate that OT induces transient increases in spontaneous GABAergic transmission by activating interneurons in the basolateral amygdala. The resultant increase in GABA release in the LA activates presynaptic GABAB receptors on both inhibitory and excitatory inputs onto LA neurons, reducing release probability at these synapses. We subsequently demonstrate that OT modulates synaptic plasticity at cortical inputs to the LA.

scholarly journals CAP2 is a novel regulator of Cofilin in synaptic plasticity and Alzheimer’s disease

2019 ◽  
Author(s):  
Silvia Pelucchi ◽  
Lina Vandermeulen ◽  
Lara Pizzamiglio ◽  
Bahar Aksan ◽  
Jing Yan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Long Term Potentiation ◽  
Actin Dynamics ◽  
Term Potentiation ◽  
Actin Turnover ◽  
Normal Spine

AbstractCofilin is one of the major regulators of actin dynamics in spines where it is required for structural synaptic plasticity. However, our knowledge of the mechanisms controlling Cofilin activity in spines remains still fragmented. Here, we describe the cyclase-associated protein 2 (CAP2) as a novel master regulator of Cofilin localization in spines. The formation of CAP2 dimers through its Cys32 is important for CAP2 binding to Cofilin and for normal spine actin turnover. The Cys32-dependent CAP2 homodimerization and association to Cofilin are triggered by long-term potentiation (LTP) and are required for LTP-induced Cofilin translocation into spines, spine remodeling and the potentiation of synaptic transmission. This mechanism is specifically affected in the hippocampus, but not in the superior frontal gyrus, of both Alzheimer’s Disease (AD) patients and APP/PS1 mice, where CAP2 is down-regulated and CAP2 dimer synaptic levels are reduced. In AD hippocampi, Cofilin preferentially associates with CAP2 monomer and is aberrantly localized in spines. Taken together, these results provide novel insights into structural plasticity mechanisms that are defective in AD.

Maternal infection and fever during late gestation are associated with altered synaptic transmission in the hippocampus of juvenile offspring rats

2008 ◽  
Vol 295 (5) ◽  
pp. R1563-R1571 ◽  
Author(s):  
Germaine C. Lowe ◽  
Giamal N. Luheshi ◽  
Sylvain Williams
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Late Gestation ◽  
Maternal Infection ◽  
Term Potentiation ◽  
Increased Risk ◽  
Near Term

Prenatal exposure to infection is known to affect brain development and has been linked to increased risk for schizophrenia. The goal of this study was to investigate whether maternal infection and associated fever near term disrupts synaptic transmission in the hippocampus of the offspring. We used LPS to mimic bacterial infection and trigger the maternal inflammatory response in near-term rats. LPS was administered to rats on embryonic days 15 and 16 and hippocampal synaptic transmission was evaluated in the offspring on postnatal days 20–25. Only offspring from rats that showed a fever in response to LPS were tested. Schaffer collateral-evoked field excitatory postsynaptic potentials (fEPSPs) and fiber volleys in CA1 of hippocampal slices appeared smaller in offspring from the LPS group compared with controls, but, when the fEPSPs were normalized to the amplitude of fiber volleys, they were larger in the LPS group. In addition, intrinsic excitability of CA1 pyramidal neurons was heightened, as antidromic field responses in the LPS group were greater than those from control. Short-, but not long-term plasticity was impaired since paired-pulse facilitation of the fEPSP was attenuated in the LPS group, whereas no differences in long-term potentiation were noted. These results suggest that LPS-induced inflammation during pregnancy produces in the offspring a reduction in presynaptic input to CA1 with compensatory enhancements in postsynaptic glutamatergic response and pyramidal cell excitability. Neurodevelopmental disruption triggered by prenatal infection can have profound effects on hippocampal synaptic transmission, likely contributing to the memory and cognitive deficits observed in schizophrenia.

scholarly journals Disinhibitory circuitry gates associative synaptic plasticity in olfactory cortex

2020 ◽  
Author(s):  
Martha Canto-Bustos ◽  
F. Kathryn Friason ◽  
Constanza Bassi ◽  
Anne-Marie M. Oswald
Keyword(s):  
Synaptic Plasticity ◽  
Pyramidal Neurons ◽  
Piriform Cortex ◽  
Inhibitory Neuron ◽  
Long Term Potentiation ◽  
Inhibitory Interneurons ◽  
Sensory Stimuli ◽  
Term Potentiation ◽  
Cortical Responses

AbstractInhibitory microcircuits play an essential role in regulating cortical responses to sensory stimuli. Interneurons that inhibit dendritic or somatic integration in pyramidal neurons act as gatekeepers for neural activity, synaptic plasticity and the formation of sensory representations. Conversely, interneurons that specifically inhibit other interneurons can open gates through disinhibition. In the rodent piriform cortex, relief of dendritic inhibition permits long-term potentiation (LTP) of the recurrent synapses between pyramidal neurons (PNs) thought to underlie ensemble odor representations. We used an optogenetic approach to identify the inhibitory interneurons and disinhibitory circuits that regulate LTP. We focused on three prominent inhibitory neuron classes-somatostatin (SST), parvalbumin (PV), and vasoactive intestinal polypeptide (VIP) interneurons. We find that VIP interneurons inhibit SST interneurons and promote LTP through subthreshold dendritic disinhibition. Alternatively, suppression of PV-interneuron inhibition promotes LTP but requires suprathreshold spike activity. Thus, we have identified two disinhibitory mechanisms to regulate synaptic plasticity during olfactory processing.

Antigen-induced long-term potentiation of nicotinic synaptic transmission in the superior cervical ganglion of the guinea pig

1995 ◽  
Vol 73 (5) ◽  
pp. 2004-2016 ◽  
Author(s):  
D. Weinreich ◽  
B. J. Undem ◽  
G. Taylor ◽  
M. F. Barry
Keyword(s):  
Synaptic Plasticity ◽  
Guinea Pig ◽  
Synaptic Transmission ◽  
Specific Antigen ◽  
Long Term Potentiation ◽  
Antigen Challenge ◽  
Lipoxygenase Inhibitors ◽  
Term Potentiation ◽  
Wide Range

1. Recordings of evoked postganglionic compound action potentials (CAPs) evoked by preganglionic stimulation were obtained from guinea pig superior cervical ganglia (SCGs) in vitro to study the effects of specific antigen challenge on ganglionic synaptic transmission. SCGs were removed from guinea pigs actively sensitized to ovalbumin. 2. Exposing SCGs from sensitized animals to the sensitizing antigen (0.01-10 micrograms/ml) for 5 min produced a sustained increase in the magnitude of the evoked CAP unaccompanied by a change in the preganglionic volley. Nonsensitizing antigens were ineffective. Also ineffective were antigens applied to nonsensitized SCG. This persistent antigen-induced increase in synaptic transmission was designated antigen-induced long-term potentiation (LTP) (A-LTP) because its duration (> 30 min) greatly outlasted posttetanic potentiation (PTP) in this ganglion. 3. A-LTP and neurogenic LTP (N-LTP) were observed to coexist in the same ganglion; the presence of one form of synaptic plasticity did not preclude the development of the other. Both phenomena were influenced by presynaptic factors: prolonged (2 h, 40 Hz) repetitive presynaptic stimulation abolished A-LTP or N-LTP but did not affect PTP. 4. By contrast to N-LTP, which requires a brief presynaptic tetanus, A-LTP could be triggered over a wide range of presynaptic stimulation (0.016-3 Hz) or even in the absence of presynaptic stimulation. 5. The amplitude and duration of A-LTP were not significantly affected by 1) H1, H2, or H3 histamine receptor antagonists added before or after antigen challenge; 2) the presence of saturating concentrations of histamine (100-300 microM); 3) the presence of specific or nonspecific lipoxygenase inhibitors or a selective cyclooxygenase inhibitor; or 4) blockade of alpha- or beta-adrenergic receptors, 5-HT3 receptors, muscarinic receptors, or glutamate receptors, or inhibition of acetylcholinesterase or protein synthesis. 6. Our results indicate that specific antigen challenge of isolated sympathetic ganglia activates resident mast cells to release substances that initiate a novel form of synaptic plasticity, an activity-independent and long-lasting increase in synaptic efficacy.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Synaptic Vesicle ◽  
Long Term Potentiation ◽  
Synaptic Dysfunction ◽  
Over Expression ◽  
Term Potentiation ◽  
Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

Sign in / Sign up

Export Citation Format

Share Document