The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The phosphoinositide PI(3,4,5)P3 is a key regulator of AMPA receptor function in the CA3-CA1 synapse of hippocampal pyramidal neurons.

Synaptic plasticity, the process widely believed to be the cellular basis of learning and memory, is defined to be the physiological change in synaptic strength that occurs in response to neuronal activity. This phenomenon is present throughout the brain but one region studied with great intensity is the hippocampus, the region responsible for the encoding of learning and the target of many neurological diseases. In the hippocampus, one of the mechanisms for modulating excitatory synaptic efficacy is the trafficking of AMPA-type glutamate receptors. Phosphoinositides are critical regulators of membrane trafficking. One of the least understood phosphoinositides for membrane trafficking in neurons is PI(3,4,5)P3. Most studies have addressed potential roles for phosphoinositide 3-kinase (PI3K), the kinase that generates PIP3 from PIP2, and its downstream effectors but have been unable to come to a consensus as to how PI3K is necessary for basal synaptic function and during synaptic plasticity. Here we present research that has focused on PIP3 as a critical regulator in synaptic function and plasticity. We have found that PIP3 plays an important role in the trafficking and/or stability of AMPA receptors at the CA3-CAI synapse. This conclusion is based on several lines of experimental evidence including electrophysiological data monitoring endogenous AMPA receptors during depletion and elevation of PIP3 levels, and ultrastructural analysis of the distribution of endogenous AMPA receptors when PIP3 is depleted. Using a probe that can report changes in PIP3 levels via FRET, we report the existence of a discrete and highly dynamic population of PIP3 at the dendritic spine, the location of the excitatory synapse. During the induction of synaptic plasticity, we have demonstrated that increases in PIP3 occur locally in the dendritic spine and can be visualized in real-time. Based on these results, we propose PIP3 is important for AMPA receptor function at the synapse and is modulated during induction of synaptic plasticity. The results presented in this work constitute the first demonstration that PIP3 is a critical regulator of the excitatory synapse.Ph.D.Biological SciencesNeurosciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/127042/2/3328753.pd

Role of phosphoinositide metabolism in synaptic transmission and plasticity in hippocampal neurons.

Peer reviewe

PTEN counteracts PIP3 upregulation in spines during NMDA-receptor-dependent long-term depression

© 2014. Phosphoinositide 3-kinase (PI3K) and PTEN have been shown to participate in synaptic plasticity during long-term potentiation (LTP) and long-term depression (LTD), respectively. Nevertheless, the dynamics of phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) and the regulation of its synthesis and degradation at synaptic compartments is far from clear. Here, we have used fluorescence resonance energy transfer (FRET) imaging to monitor changes in PIP3 levels in dendritic spines from CA1 hippocampal neurons under basal conditions and upon induction of NMDA receptor (NMDAR)-dependent LTD and LTP. We found that PIP3 undergoes constant turnover in dendritic spines. Contrary to expectations, both LTD and LTP induction trigger an increase in PIP3 synthesis, which requires NMDARs and PI3K activity. Using biochemical methods, the upregulation of PIP3 levels during LTP was estimated to be twofold. However, in the case of LTD, PTEN activity counteracts the increase in PIP3 synthesis, resulting in no net change in PIP3 levels. Therefore, both LTP and LTD signaling converge towards PIP3 upregulation, but PTEN acts as an LTD-selective switch that determines the outcome of PIP3 accumulation.The Spanish Ministry [grant numbers CSD-2010-00045 and SAF-2011-24730]; and Fundación Ramón ArecesPeer Reviewe

Phosphoinositide control of postsynaptic AMPA receptor trafficking.

Peer reviewe

PI(3,4,5)P3-dependent regulation of AMPA receptor synaptic function.

Peer reviewe

The phosphoinositide PI(3,4,5)P3 is a regulator of postsynaptic AMPA receptor trafficking.

Peer reviewe

Retinoic Acid and LTP Recruit Postsynaptic AMPA Receptors Using Distinct SNARE-Dependent Mechanisms

Retinoic acid (RA)-dependent homeostatic plasticity and NMDA receptor-dependent long-term potentiation (LTP), a form of Hebbian plasticity, both enhance synaptic strength by increasing the abundance of postsynaptic AMPA receptors (AMPARs). However, it is unclear whether the molecular mechanisms mediating AMPAR trafficking during homeostatic and Hebbian plasticity differ, and it is unknown how RA signaling impacts Hebbian plasticity. Here, we show that RA increases postsynaptic AMPAR abundance using an activity-dependent mechanism that requires a unique SNARE (soluble NSF-attachment protein receptor)-dependent fusion machinery different from that mediating LTP. Specifically, RA-induced AMPAR trafficking did not involve complexin, which activates SNARE complexes containing syntaxin-1 or -3, but not complexes containing syntaxin-4, whereas LTP required complexin. Moreover, RA-induced AMPAR trafficking utilized the Q-SNARE syntaxin-4, whereas LTP utilized syntaxin-3; both additionally required the Q-SNARE SNAP-47 and the R-SNARE synatobrevin-2. Finally, acute RA treatment blocked subsequent LTP expression, probably by increasing AMPAR trafficking. Thus, RA-induced homeostatic plasticity involves a novel, activity-dependent postsynaptic AMPAR-trafficking pathway mediated by a unique SNARE-dependent fusion machinery.The work was supported by NIH grants MH086403 (L.C., R.C.M., and T.C.S.) and MH091193 (L.C.).Peer reviewe

Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome.

Fragile X syndrome (FXS) is an X chromosome-linked disease associated with severe intellectual disabilities. Previous studies using th