scholarly journals Anesthesia and Surgery Induce a Functional Decrease Selectively in Excitatory Synaptic Transmission in Mouse Prefrontal Cortex Neurons

2020 ◽  
Author(s):  
Yu Matsumoto ◽  
Yuji Fujino ◽  
Hidemasa Furue
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Cognitive Processes ◽  
Postoperative Delirium ◽  
Pyramidal Neurons ◽  
Functional Changes ◽  
Whole Cell Patch Clamp ◽  
Glutamate Receptor Antagonists ◽  
Plastic Change ◽  
Synaptic Responses

Abstract Postoperative delirium (POD), a syndrome of confusion and inattention, frequently occurs after anesthesia and surgery. However, the neuropathogenesis of POD remains mostly unknown. The prefrontal cortex (PFC) plays an essential role in cognitive processes. We therefore investigated how anesthesia and surgery induce neurofunctional changes in the PFC, and assessed whether intraoperative administration of dexmedetomidine, an alpha-2 agonist, could prevent the functional changes in the PFC. Laparotomy was performed in mice under isoflurane anesthesia. After a battery of behavioral tests measuring natural behaviors and learning and anxiety levels, PFC neuronal activities were recorded using whole-cell patch-clamp recordings. Effects of intraoperative dexmedetomidine were also examined. In the anesthesia/surgery group, the frequency of excitatory synaptic responses in PFC pyramidal neurons was decreased after the surgery without any changes in the response kinetics. On the other hand, neuronal intrinsic properties and inhibitory synaptic responses were not changed. Intraoperative dexmedetomidine or glutamate receptor antagonists, prevented the excitatory synaptic dysfunction induced by anesthesia and surgery. These findings suggest that anesthesia and surgery induce functional reductions selectively in excitatory synaptic responses in PFC pyramidal neurons, and intraoperative dexmedetomidine inhibits the plastic change in the PFC synaptic transmission.

scholarly journals Impact of subthreshold membrane potential on synaptic responses at dendritic spines of layer 5 pyramidal neurons in the prefrontal cortex

2014 ◽  
Vol 111 (10) ◽  
pp. 1960-1972 ◽  
Author(s):  
Hannah J. Seong ◽  
Rudy Behnia ◽  
Adam G. Carter
Keyword(s):  
Prefrontal Cortex ◽  
Membrane Potential ◽  
Nmda Receptors ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
K Channels ◽  
Two Photon ◽  
Synaptic Potentials ◽  
Ampa And Nmda Receptors ◽  
Synaptic Responses

Glutamatergic inputs onto cortical pyramidal neurons are received and initially processed at dendritic spines. AMPA and NMDA receptors generate both synaptic potentials and calcium (Ca) signals in the spine head. These responses can in turn activate a variety of Ca, sodium (Na), and potassium (K) channels at spines. In principle, the roles of these receptors and channels can be strongly regulated by the subthreshold membrane potential. However, the impact of different receptors and channels has usually been studied at the level of dendrites. Much less is known about their influence at spines, where synaptic transmission and plasticity primarily occur. Here we examine single-spine responses in the basal dendrites of layer 5 pyramidal neurons in the mouse prefrontal cortex. Using two-photon microscopy and two-photon uncaging, we first show that synaptic potentials and Ca signals differ at resting and near-threshold potentials. We then determine how subthreshold depolarizations alter the contributions of AMPA and NMDA receptors to synaptic responses. We show that voltage-sensitive Ca channels enhance synaptic Ca signals but fail to engage small-conductance Ca-activated K (SK) channels, which require greater numbers of inputs. Finally, we establish how the subthreshold membrane potential controls the ability of voltage-sensitive Na channels and K channels to influence synaptic responses. Our findings reveal how subthreshold depolarizations promote electrical and biochemical signaling at dendritic spines by regulating the contributions of multiple glutamate receptors and ion channels.

scholarly journals Age-dependent actions of dopamine on inhibitory synaptic transmission in superficial layers of mouse prefrontal cortex

2013 ◽  
Vol 109 (5) ◽  
pp. 1323-1332 ◽  
Author(s):  
Kush Paul ◽  
Charles L. Cox
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
D2 Receptor ◽  
Early Time ◽  
Inhibitory Response ◽  
Cellular Level ◽  
Inhibitory Synaptic Transmission ◽  
Time Period

Numerous developmental changes in the nervous system occur during the first several weeks of the rodent lifespan. Therefore, many characteristics of neuronal function described at the cellular level from in vitro slice experiments conducted during this early time period may not generalize to adult ages. We investigated the effect of dopamine (DA) on inhibitory synaptic transmission in superficial layers of the medial prefrontal cortex (PFC) in prepubertal [postnatal age (P; days) 12–20], periadolescent (P30–48), and adult (P70–100) mice. The PFC is associated with higher-level cognitive functions, such as working memory, and is associated with initiation, planning, and execution of actions, as well as motivation and cognition. It is innervated by DA-releasing fibers that arise from the ventral tegmental area. In slices from prepubertal mice, DA produced a biphasic modulation of inhibitory postsynaptic currents (IPSCs) recorded in layer II/ III pyramidal neurons. Activation of D2-like receptors leads to an early suppression of the evoked IPSC, which was followed by a longer-lasting facilitation of the IPSC mediated by D1-like DA receptors. In periadolescent mice, the D2 receptor-mediated early suppression was significantly smaller compared with the prepubertal animals and absent in adult animals. Furthermore, we found significant differences in the DA-mediated lasting enhancement of the inhibitory response among the developmental groups. Our findings suggest that behavioral paradigms that elicit dopaminergic release in the PFC differentially modulate inhibition of excitatory pyramidal neuron output in prepuberty compared with periadolescence and adulthood in the superficial layers (II/III) of the cortex.

Reduced Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Neurons in the Medial Prefrontal Cortex in a Mouse Model of Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Xiao-Qin Zhang ◽  
Le Xu ◽  
Si-Yu Yang ◽  
Lin-Bo Hu ◽  
Fei-Yuan Dong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Intrinsic Excitability ◽  
Rodent Models ◽  
Morphological Complexity ◽  
Sholl Analysis ◽  
Model Of Alzheimer’S Disease

Background: Abnormal morphology and function of neurons in the prefrontal cortex (PFC) are associated with cognitive deficits in rodent models of Alzheimer’s disease (AD), particularly in cortical layer-5 pyramidal neurons that integrate inputs from different sources and project outputs to cortical or subcortical structures. Pyramidal neurons in layer-5 of the PFC can be classified as two subtypes depending on the inducibility of prominent hyperpolarization-activated cation currents (h-current). However, the differences in the neurophysiological alterations between these two subtypes in rodent models of AD remain poorly understood. Objective: To investigate the neurophysiological alterations between two subtypes of pyramidal neurons in hAPP-J20 mice, a transgenic model for early onset AD. Methods: The synaptic transmission and intrinsic excitability of pyramidal neurons were investigated using whole-cell patch recordings. The morphological complexity of pyramidal neurons was detected by biocytin labelling and subsequent Sholl analysis. Results: We found reduced synaptic transmission and intrinsic excitability of the prominent h-current (PH) cells but not the non-PH cells in hAPP-J20 mice. Furthermore, the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels which mediated h-current was disrupted in the PH cells of hAPP-J20 mice. Sholl analysis revealed that PH cells had less dendritic intersections in hAPP-J20 mice comparing to control mice, implying that a lower morphological complexity might contribute to the reduced neuronal activity. Conclusion: These results suggest that the PH cells in the medial PFC may be more vulnerable to degeneration in hAPP-J20 mice and play a sustainable role in frontal dysfunction in AD.

scholarly journals Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Sacai ◽  
Kazuto Sakoori ◽  
Kohtarou Konno ◽  
Kenichiro Nagahama ◽  
Honoka Suzuki ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Social Interaction ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Spectrum Disorder ◽  
Excitatory Synaptic Transmission ◽  
Layer 2

Abstract Autism spectrum disorder (ASD) is thought to result from deviation from normal development of neural circuits and synaptic function. Many genes with mutation in ASD patients have been identified. Here we report that two molecules associated with ASD susceptibility, contactin associated protein-like 2 (CNTNAP2) and Abelson helper integration site-1 (AHI1), are required for synaptic function and ASD-related behavior in mice. Knockdown of CNTNAP2 or AHI1 in layer 2/3 pyramidal neurons of the developing mouse prefrontal cortex (PFC) reduced excitatory synaptic transmission, impaired social interaction and induced mild vocalization abnormality. Although the causes of reduced excitatory transmission were different, pharmacological enhancement of AMPA receptor function effectively restored impaired social behavior in both CNTNAP2- and AHI1-knockdown mice. We conclude that reduced excitatory synaptic transmission in layer 2/3 pyramidal neurons of the PFC leads to impaired social interaction and mild vocalization abnormality in mice.

scholarly journals Loss of microRNAs in pyramidal neurons leads to specific changes in inhibitory synaptic transmission in the prefrontal cortex

2012 ◽  
Vol 50 (3-4) ◽  
pp. 283-292 ◽  
Author(s):  
Ruby Hsu ◽  
Claude M. Schofield ◽  
Cassandra G. Dela Cruz ◽  
Dorothy M. Jones-Davis ◽  
Robert Blelloch ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Inhibitory Synaptic Transmission

Differential Ethanol Sensitivity of Subpopulations of GABAA Synapses Onto Rat Hippocampal CA1 Pyramidal Neurons

1997 ◽  
Vol 77 (3) ◽  
pp. 1306-1312 ◽  
Author(s):  
J. L. Weiner ◽  
C. Gu ◽  
T. V. Dunwiddie
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Decay Rates ◽  
Receptor Subunit ◽  
Ethanol Sensitivity ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Synaptic Responses

Weiner, J. L., C. Gu, and T. V. Dunwiddie. Differential ethanol sensitivity of subpopulations of GABAA synapses onto rat hippocampal CA1 pyramidal neurons. J. Neurophysiol. 77: 1306–1312, 1997. The actions of ethanol on γ-aminobutyric acid-A (GABAA) receptor-mediated synaptic transmission in rat hippocampal CA1 neurons remain controversial. Recent studies have reported that intoxicating concentrations of ethanol (10–100 mM) can potentiate, inhibit, or have no effect on GABAA receptor-mediated synaptic responses in this brain region. The essential determinants of ethanol sensitivity have not been defined; however, GABAA receptor subunit composition, as well as posttranslational modifications of these receptors, have been suggested as important factors in conferring ethanol sensitivity to the GABAA receptor complex. Multiple types of GABAA receptor-mediated synaptic responses have been described within individual hippocampal CA1 neurons. These responses have been shown to differ in some of their physiological and pharmacological properties. In the present study we tested the hypothesis that some of the disparate findings concerning the effects of ethanol may have resulted from differences in the ethanol sensitivity of GABAA receptor-mediated synapses on single CA1 pyramidal cells. Electrical stimulation adjacent to the stratum pyramidale (proximal) and within the stratum lacunosum-moleculare (distal) activated nonoverlapping populations of GABAA receptors on rat hippocampal CA1 neurons. Proximal inhibitory postsynaptic currents (IPSCs) decayed with a single time constant and were significantly potentiated by ethanol at all concentrations tested (40, 80, and 160 mM). Distal IPSCs had slower decay rates that were often described better by the sum of two exponentials and were significantly less sensitive to ethanol at all concentrations tested. Three other allosteric modulators of GABAA receptor function with well-defined GABAA receptor subunit requirements, pentobarbital, flunitrazepam, and zolpidem, potentiated proximal and distal GABAA IPSCs to the same extent. These results demonstrate that the ethanol sensitivity of GABAA receptors can differ, not only between brain regions but within single neurons. These findings offer a possible explanation for the conflicting results of previous studies on ethanol modulation of GABAA receptor-mediated synaptic transmission in rat hippocampal CA1 neurons.

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