Synaptic proteins in the hippocampus indicative of increased neuronal activity in CA3 in schizophrenia.
نویسندگان
چکیده
OBJECTIVE In schizophrenia, hippocampal perfusion is increased and declarative memory function is degraded. Based on an a priori model of hippocampal dysfunction in schizophrenic psychosis, the authors postulated molecular and cellular changes in CA3 consistent with increased NMDA receptor signaling. METHOD Postmortem hippocampal subfield tissue (CA3, CA1) from subjects with schizophrenia and nonpsychiatric comparison subjects was analyzed using Western blotting and Golgi histochemistry to examine the hypothesized outcomes. RESULTS The GluN2B-containing NMDA receptors (GluN2B/GluN1) and their associated postsynaptic membrane protein PSD95 were both increased in schizophrenia in CA3 tissue, but not in CA1 tissue. Quantitative analyses of Golgi-stained hippocampal neurons showed an increase in spine density on CA3 pyramidal cell apical dendrites (stratum radiatum) and an increase in the number of thorny excrescences. CONCLUSIONS The hippocampal data are consistent with increased excitatory signaling in CA3 and/or with an elevation in silent synapses in CA3, a state that may contribute to an increase in long-term potentiation in CA3 with subsequent stimulation and "unsilencing." These changes are plausibly associated with increased associational activity in CA3, with degraded declarative memory function, and with formation of false memories with psychotic content. The influence of these hyperactive hippocampal projections on targets in the limbic neocortex could contribute to components of schizophrenia manifestations in other cerebral regions.
منابع مشابه
GABA-mediated membrane oscillations as coincidence detectors for enhancing synaptic efficacy in the developing hippocampus
Spontaneously occurring neuronal oscillations constitute a hallmark of developmental networks. They have been observed in the retina, neocortex, hippocampus, thalamus and spinal cord. In the immature hippocampus the so-called ‘giant depolarizing potentials’ (GDPs) are network-driven membrane oscillations characterized by recurrent membrane depolarization with superimposed fast action potentials...
متن کاملGABA-mediated membrane oscillations as coincidence detectors for enhancing synaptic efficacy in the developing hippocampus
Spontaneously occurring neuronal oscillations constitute a hallmark of developmental networks. They have been observed in the retina, neocortex, hippocampus, thalamus and spinal cord. In the immature hippocampus the so-called ‘giant depolarizing potentials’ (GDPs) are network-driven membrane oscillations characterized by recurrent membrane depolarization with superimposed fast action potentials...
متن کاملEffect of insulin and L-ascorbic acid on rate of neuronal apoptosis in dentate gyrus and CA3 region of hippocampus in type 1 diabetic rats
Introduction: The aim of this study was to determine the effects of Insulin and Lascorbic acid on prevention of neuronal in granular layer of dentate gyrus and pyramidal layer of CA3 of hippocampus in streptozotocin-Induced diabetic rats. Methods: In this experimental study, diabetes type 1 was included by a single intraperitoneal injection of streptozotocin (STZ) (60mg/kg) in male adult ...
متن کاملCharacterization of spontaneous network-driven synaptic activity in rat hippocampal slice cultures
A particular characteristic of the neonatal hippocampus is the presence of spontaneous network-driven oscillatory events, the so-called giant depolarizing potentials (GDPs). GDPs depend on the interplay between GABA and glutamate. Early in development, GABA, acting on GABAA receptors, depolarizes neuronal membranes via a Cl- efflux. Glutamate, via AMPA receptors, generates a positive feedback n...
متن کاملDevelopmental effect of light deprivation on synaptic plasticity of rats' hippocampus: implications for melatonin
Objective(s): There are few reports have demonstrated the effect of a change-in-light experience on the structure and function of hippocampus. A change-in-light experience also affects the circadian pattern of melatonin secretion. This study aimed to investigate developmental effect of exogenous melatonin on synaptic plasticity of hippocampus of light deprived rats. Materials and Methods: The ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The American journal of psychiatry
دوره 172 4 شماره
صفحات -
تاریخ انتشار 2015