Electromagnetic Field Effect or Simply Stress? Effects of UMTS Exposure on Hippocampal Longterm Plasticity in the Context of Procedure Related Hormone Release

Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded

Successful Cognitive Aging in Rats: A Role for mGluR5 Glutamate Receptors, Homer 1 Proteins and Downstream Signaling Pathways

Normal aging is associated with impairments in cognition, especially learning and memory. However, major individual differences are known to exist. Using the classical Morris Water Maze (MWM) task, we discriminated a population of 24-months old Long Evans aged rats in two groups - memory-impaired (AI) and memory-unimpaired (AU) in comparison with 6-months old adult animals. AI rats presented deficits in learning, reverse memory and retention. At the molecular level, an increase in metabotropic glutamate receptors 5 (mGluR5) was observed in post-synaptic densities (PSD) in the hippocampus of AU rats after training. Scaffolding Homer 1b/c proteins binding to group 1 mGluR facilitate coupling with its signaling effectors while Homer 1a reduces it. Both Homer 1a and 1b/c levels were up-regulated in the hippocampus PSD of AU animals following MWM task. Using immunohistochemistry we further demonstrated that mGluR5 as well as Homer 1b/c stainings were enhanced in the CA1 hippocampus sub-field of AU animals. In fact mGluR5 and Homer 1 isoforms were more abundant and co-localized in the hippocampal dendrites in AU rats. However, the ratio of Homer 1a/Homer 1b/c bound to mGluR5 in the PSD was four times lower for AU animals compared to AI rats. Consequently, AU animals presented higher PKCγ, ERK, p70S6K, mTOR and CREB activation. Finally the expression of immediate early gene Arc/Arg3.1 was shown to be higher in AU rats in accordance with its role in spatial memory consolidation. On the basis of these results, a model of successful cognitive aging with a critical role for mGluR5, Homer 1 proteins and downstream signalling pathways is proposed here

NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation

How neuronal proteomes self-organize is poorly understood because of their inherent molecular and cellular complexity. Here, focusing on mammalian synapses we use blue-native PAGE and ‘gene-tagging’ of GluN1 to report the first biochemical purification of endogenous NMDA receptors (NMDARs) directly from adult mouse brain. We show that NMDARs partition between two discrete populations of receptor complexes and B1.5MDa supercomplexes. We tested the assembly mechanism with six mouse mutants, which indicates a tripartite requirement of GluN2B, PSD93 and PSD95 gate the incorporation of receptors into B1.5MDa supercomplexes, independent of either canonical PDZ-ligands or GluN2A. Supporting the essential role of GluN2B, quantitative gene-tagging revealed a fourfold molar excess of GluN2B over GluN2A in adult forebrain. NMDAR supercomplexes are assembled late in postnatal development and triggered by synapse maturation involving epigenetic and activity-dependent mechanisms. Finally, screening the quaternary organization of 60 native proteins identified numerous discrete supercomplexes that populate the mammalian synapse

Arc-dependent synapse-specific homeostatic plasticity

Both theoretical and experimental research has indicated that the synaptic strength between neurons in a network needs to be properly fine-tuned and controlled by homeostatic mechanisms to ensure proper network function. One such mechanism that has been extensively characterized is synaptic homeostatic plasticity or global synaptic scaling. This mechanism refers to the bidirectional ability of all synapses impinging on a neuron to actively compensate for changes in the neuron's overall excitability. Here, using a combination of electrophysiological, two-photon glutamate uncaging and imaging methods, we show that mature individual synapses, independent of neighboring synapses, have the ability to autonomously sense their level of activity and actively compensate for it in a homeostatic-like fashion. This synapse-specific homeostatic plasticity, similar to global synaptic plasticity, requires the immediate early gene Arc. Together, our results document an extra level of regulation of synaptic function that bears important computational consequences on information storage in the brain