Dr Bhagya V (Senior Research Associate) presented her journal club on the topic "The AAA+ ATPase Thorase Regulates AMPA Receptor-Dependent Synaptic Plasticity and Behavior" by Jianmin Zhang et al from Cell, April 2011.

SUMMARY
The synaptic insertion or removal of AMPA receptors (AMPAR) plays critical roles in the regulation of synaptic activity reflected in the expression of long-term potentiation (LTP) and long-term depression (LTD). The cellular events underlying this important process in learning and memory are still being revealed. Here we describe and characterize the AAA + ATPa se Thorase, which regulates the expression of surface AMPAR. In an ATPase-dependent manner Thorase mediates the internalization of AMPAR by disassembling the AMPAR-GR IP1 complex. Following genetic deletion of Thorase , the internalization of AMPAR is substantially reduced, leading to increased amplitudes of miniature excitatory postsynaptic currents, enhancement of LTP, and elimination of LTD. These molecular events are expressed as deficits in learning and memory in Thorase null mice. This study identifies an AAA + ATPase that plays a critical role in regulating the surface expression of AMPAR and thereby regulates synaptic plasticity and learning and memory.

Dr. V Bhagya (Senior Research Associate) presented the first concept seminar of the year on the topic "Is LTP = Memory?"

She started with a detailed overview of LTP formation, she narrowed down to LTP in NMDA receptors in CA1 region of the hippocampus. She discussed several early papers starting with the Morris water maze test in 1984 that supported the hypothesis that learning and memory could indeed be directly correlated to LTP. These papers demonstrated that blocking of NMDAR or some of its subunits (NR2B) lead to learning impairment. 

She then discussed several later papers that show that there is no direct correlation. For example, severe early life stress (24 hour maternal separation in neonatal rodents) hampers learning and neurogenesis but improves hippocampal plasticity under high stress for adults. LTP is also seen in other areas (eg: addiction to cocaine, nicotine causes LTP in the VTA). 

The current status of research seems to indicate that LTP is perhaps necessary but not sufficient in the memory formation and retrieval processes. 

The seminar provoked plenty of lively interactions - some hypothetical questions, some comments targeted to the topic and on the various experimental approaches taken up in the papers. 

"Does the brain prefer oscillatory stimuli or LTP type of stereotyped inputs?",  
"Interpretation of data based on Gene knockouts needs to be done with care as there is significant impact on  aspects of functioning other than the one under study."
"Isn't focus on NMDA too simplistic as it is involved in many other activities for normal functioning?" 
"What about learning aspects outside the hippocampus - involving the cortices?"  

Overall, great coverage of the topic and a stimulating debate on its different aspects.

Pradeep Mishra (1st year PhD Scholar) presented his journal club on 20th Aug on "Loss of activity-induced phosphorylation of MeCP2 enhances synaptogenesis, LTP and spatial memory" by Hongda Li et al, Nature Neuroscience (August 2011), Vol. 14,Pg: 1001–1008. 

ABSTRACT
DNA methylation–dependent epigenetic mechanisms underlie the development and function of the mammalian brain. MeCP2 is highly expressed in neurons and functions as a molecular linker between DNA methylation, chromatin remodeling and transcription regulation. Previous in vitro studies have shown that neuronal activity–induced phosphorylation (NAIP) of methyl CpG–binding protein 2 (MeCP2) precedes its release from the Bdnf promoter and the ensuing Bdnf transcription. However, the in vivo function of this phosphorylation event remains elusive. We generated knock-in mice that lack NAIP of MeCP2 and found that they performed better in hippocampus-dependent memory tests, presented enhanced long-term potentiation at two synapses in the hippocampus and showed increased excitatory synaptogenesis. At the molecular level, the phospho-mutant MeCP2 protein bound more tightly to several MeCP2 target gene promoters and altered the expression of these genes. Our results suggest that NAIP of MeCP2 is required for modulating dynamic functions of the adult mouse brain.