Synaptic transmission is essential for early development of the central nervous system. However, the mechanisms that regulate early synaptic transmission in the cerebral cortex are unclear. PKMζ is a kinase essential for the maintenance of LTP. We show for the first time that inhibition of PKMζ produces a profound depression of basal synaptic transmission in neonatal, but not adult, rat perirhinal cortex. This suggests that synapses in early development are in a constitutive LTP-like state. Furthermore, basal synaptic transmission in immature, but not mature, perirhinal cortex relies on persistent activity of metabotropic glutamate (mGlu) receptor, PI3Kinase and mammalian target of rapamycin (mTOR). Thus early in development, cortical synapses exist in an LTP-like state maintained by tonically active mGlu receptor-, mTOR- and PKMζ- dependent cascades. These results provide new understanding of the molecular mechanisms that control synapses during development and may aid our understanding of developmental disorders such as autism and schizophrenia. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
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http://dx.doi.org/10.1016/j.neuropharm.2012.03.010 | DOI Listing |
Pharmacol Res
January 2025
Gill Institute for Neuroscience; Dept. of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405. Electronic address:
Δ-tetrahydrocannabinol (THC), the chief psychoactive ingredient of cannabis, acts in the brain primarily via cannabinoid CB1 receptors. These receptors are implicated in several forms of synaptic plasticity - depolarization-induced suppression of excitation (DSE), metabotropic suppression of excitation (MSE), long term depression (LTD) and activation-dependent desensitization. Cultured autaptic hippocampal neurons express all of these, illustrating the rich functional and temporal heterogeneity of CB1 at a single set of synapses.
View Article and Find Full Text PDFNeuroscience
January 2025
Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, China; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, China; College of Life Science, Shaanxi Normal University, Xi'an, China. Electronic address:
Several studies indicate that fructose can be used as an energy source for subterranean rodents. However, how subterranean rodents utilize fructose metabolism with no apparent physiological drawbacks remains poorly understood. In the present study, we measured field excitatory postsynaptic potentials (fEPSPs) in hippocampal slices from Gansu zokor and SD rats hippocampi before and 60 min after replacement of 10 mM glucose in the artificial cerebrospinal fluid (ACSF) with 10 mM fructose (gassed with 95 % O and 5 % CO).
View Article and Find Full Text PDFSci Adv
January 2025
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The pathophysiology of neurodevelopmental disorders involves vulnerable neural populations, including striatal circuitry, and convergent molecular nodes, including chromatin regulation and synapse function. Despite this, how epigenetic regulation regulates striatal development is understudied. Recurrent de novo mutations in are associated with intellectual disability and autism.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710000, China.
Neurotransmitters and neuromodulators can be released via either action potential (AP)-evoked transient or AP-independent continuous neurotransmission. The elevated AP-evoked neurotransmission in the primary sensory neurons plays crucial roles in hyperalgesia. However, whether and how the AP-independent continuous neurotransmission contributes to hyperalgesia remains largely unknown.
View Article and Find Full Text PDFArch Rehabil Res Clin Transl
December 2024
Peninsula Hospital Center, Department of Speech-Language Pathology and Audiology, Far Rockaway, NY.
Objective: To determine if fatigue systematically effects the timing of swallowing events and to discuss underlying causes of fatigue other than peripheral neuromuscular fatigue.
Design: Pre-post within-subject repeated-measures design.
Setting: General acute care hospital and designated stroke center.
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