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

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.

scholarly journals Mu-opioids suppress GABAergic synaptic transmission onto orbitofrontal cortex pyramidal neurons with subregional selectivity

2020 ◽  
Author(s):  
Benjamin K. Lau ◽  
Brittany P. Ambrose ◽  
Catherine S. Thomas ◽  
Min Qiao ◽  
Stephanie L. Borgland
Keyword(s):  
Synaptic Transmission ◽  
Opioid Receptor ◽  
Orbitofrontal Cortex ◽  
Pyramidal Neurons ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Inhibitory Synaptic Transmission ◽  
Receptor Coupling ◽  
Mu Opioids ◽  
Gabaergic Synaptic Transmission

AbstractThe orbitofrontal cortex (OFC) plays a critical role in evaluating outcomes in a changing environment. Administering opioids to the OFC can alter the hedonic reaction to food rewards and increase their consumption in a subregion specific manner. However, it is unknown how mu-opioid signalling influences synaptic transmission in the OFC. Thus, we investigated the cellular actions of mu-opioids within distinct subregions of the OFC. Using in-vitro patch clamp electrophysiology in brain slices containing the OFC, we found that the mu-opioid agonist, DAMGO produced a concentration-dependant inhibition of GABAergic synaptic transmission onto medial OFC (mOFC), but not lateral OFC (lOFC) neurons. This effect was mediated by presynaptic mu-opioid receptor activation of local parvalbumin (PV+)-expressing interneurons. The DAMGO-induced suppression of inhibition was long-lasting and not reversed upon washout of DAMGO, or by application of the mu-opioid receptor antagonist, CTAP, suggesting an inhibitory long-term depression (iLTD) induced by an exogenous mu-opioid. We show that LTD at inhibitory synapses is dependent on downstream cAMP/PKA signaling, which differs between the mOFC and lOFC. Finally, we demonstrate that endogenous opioid release triggered via moderate physiological stimulation can induce LTD. Taken together, these results suggest that presynaptic mu-opioid stimulation of local PV+ interneurons induces a long-lasting suppression of GABAergic synaptic transmission, which depends on subregional differences in mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascade. These findings provide mechanistic insight into the opposing functional effects produced by mu-opioids within the OFC.Significance StatementConsidering that both the OFC and the opioid system regulate reward, motivation, and food intake; understanding the role of opioid signaling within the OFC is fundamental for a mechanistic understanding of the sequelae for several psychiatric disorders. This study makes several novel observations. First, mu-opioids induce a long-lasting suppression of inhibitory synaptic transmission onto OFC pyramidal neurons in a regionally selective manner. Secondly, mu-opioids recruit PV+ inputs to suppress inhibitory synaptic transmission in the mOFC. Thirdly, the regional selectivity of mu-opioid action of endogenous opioids is due to the efficacy of mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascades. These experiments are the first to reveal a cellular mechanism of opioid action within the OFC.

scholarly journals Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus

2020 ◽  
Vol 295 (25) ◽  
pp. 8589-8595 ◽  
Author(s):  
Motokazu Uchigashima ◽  
Ming Leung ◽  
Takuya Watanabe ◽  
Amy Cheung ◽  
Timmy Le ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Single Cell ◽  
Pyramidal Neurons ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Dependent Manner ◽  
Splice Isoforms ◽  
Inhibitory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons

Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, trans-synaptic protein–protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry, and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that the NLGN3 protein differentially regulates inhibitory synaptic transmission in a splice isoform–dependent manner at hippocampal CA1 synapses. We also found that distinct subcellular localizations of the NLGN3 isoforms contribute to the functional differences observed among these isoforms. Finally, results from single-cell RNA-Seq analyses revealed that Nlgn1 and Nlgn3 are the major murine Nlgn genes and that the expression levels of the Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons. Our results delineate isoform-specific effects of Nlgn genes on the E-I balance in the murine hippocampus.

scholarly journals Latrophilin-2 and latrophilin-3 are redundantly essential for parallel-fiber synapse function in cerebellum

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Roger Shen Zhang ◽  
Kif Liakath-Ali ◽  
Thomas C Südhof
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Pyramidal Neurons ◽  
Bergmann Glia ◽  
Parallel Fiber ◽  
Excitatory Synapses ◽  
Inhibitory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons ◽  
Double Deletion

Latrophilin-2 (Lphn2) and latrophilin-3 (Lphn3) are adhesion GPCRs that serve as postsynaptic recognition molecules in CA1 pyramidal neurons of the hippocampus, where they are localized to distinct dendritic domains and are essential for different sets of excitatory synapses. Here, we studied Lphn2 and Lphn3 in the cerebellum. We show that latrophilins are abundantly and differentially expressed in the cerebellar cortex. Using conditional KO mice, we demonstrate that the Lphn2/3 double-deletion but not the deletion of Lphn2 or Lphn3 alone suppresses parallel-fiber synapses and reduces parallel-fiber synaptic transmission by ~50% without altering release probability. Climbing-fiber synapses, conversely, were unaffected. Even though ~50% of total cerebellar Lphn3 protein is expressed in Bergmann glia, Lphn3 deletion from Bergmann glia did not detectably impair excitatory or inhibitory synaptic transmission. Our studies demonstrate that Lphn2 and Lphn3 are selectively but redundantly required in Purkinje cells for parallel-fiber synapses.

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.

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