Toxoplasma gondii Infection of Alzheimer's Disease Mice Reduces Brain Amyloid Density Globally and Regionally.

Background: Toxoplasma gondii infection of Alzheimer's disease model mice decreases amyloid β plaques. We aimed to determine if there is a brain regional difference in amyloid β reduction in the brains of T. gondii-infected compared to control mice.

Inhibition of PDE2 and PDE4 synergistically improves memory consolidation processes.

Phosphodiesterases (PDE) are the only enzymes that degrade cAMP and cGMP which are second messengers crucial to memory consolidation. Different PDE inhibitors have been developed and tested for their memory-enhancing potential, but the occurrence of side effects has hampered clinical progression. As separate inhibition of the PDE2 and PDE4 enzyme family has been shown to enhance memory, we investigated whether concurrent treatment with a PDE2 and PDE4 inhibitor can have synergistic effects on memory consolidation processes.

PDE4D regulates Spine Plasticity and Memory in the Retrosplenial Cortex.

The retrosplenial cortex (RSC) plays a critical role in episodic memory, but the molecular mechanisms governing plasticity in this structure are poorly understood. Diverse studies have demonstrated a role for RSC in acquisition, early consolidation and retrieval similar to the hippocampus (HC), as well as in systems consolidation similar to the anterior cingulate cortex. Here, we asked whether established molecular and structural substrates of memory consolidation in the HC also engage in RSC shortly after learning.

Everyday memory: towards a translationally effective method of modelling the encoding, forgetting and enhancement of memory.

The testing of cognitive enhancers could benefit from the development of novel behavioural tasks that display better translational relevance for daily memory and permit the examination of potential targets in a within-subjects manner with less variability. We here outline an optimized spatial 'everyday memory' task. We calibrate it systematically by interrogating certain well-established determinants of memory and consider its potential for revealing novel features of encoding-related gene activation.

The PDE4 inhibitor HT-0712 improves hippocampus-dependent memory in aged mice.

Aging is associated with declines in memory and cognitive function. Here, we evaluate the effects of HT-0712 on memory formation and on cAMP response element-binding protein (CREB)-regulated genes in aged mice. HT-0712 enhanced long-term memory formation in normal young mice at brain concentrations similar to those found to increase CRE-mediated gene expression in hippocampal neurons.

Ca(V)1 and Ca(V)2 channels engage distinct modes of Ca(2+) signaling to control CREB-dependent gene expression.

Activity-dependent gene expression triggered by Ca(2+) entry into neurons is critical for learning and memory, but whether specific sources of Ca(2+) act distinctly or merely supply Ca(2+) to a common pool remains uncertain. Here, we report that both signaling modes coexist and pertain to Ca(V)1 and Ca(V)2 channels, respectively, coupling membrane depolarization to CREB phosphorylation and gene expression. Ca(V)1 channels are advantaged in their voltage-dependent gating and use nanodomain Ca(2+) to drive local CaMKII aggregation and trigger communication with the nucleus.

Excitation-transcription coupling in sympathetic neurons and the molecular mechanism of its initiation.

In excitable cells, membrane depolarization and activation of voltage-gated Ca²+ (Ca(V)) channels trigger numerous cellular responses, including muscle contraction, secretion, and gene expression. Yet, while the mechanisms underlying excitation-contraction and excitation-secretion coupling have been extensively characterized, how neuronal activity is coupled to gene expression has remained more elusive. In this article, we will discuss recent progress toward understanding the relationship between patterns of channel activity driven by membrane depolarization and activation of the nuclear transcription factor CREB.

Uncoupling dendrite growth and patterning: single-cell knockout analysis of NMDA receptor 2B.

N-methyl-D-aspartate receptors (NMDARs) play important functions in neural development. NR2B is the predominant NR2 subunit of NMDAR in the developing brain. Here we use mosaic analysis with double markers (MADM) to knock out NR2B in isolated single cells and analyze its cell-autonomous function in dendrite development.

CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation-transcription coupling.

Communication between cell surface proteins and the nucleus is integral to many cellular adaptations. In the case of ion channels in excitable cells, the dynamics of signaling to the nucleus are particularly important because the natural stimulus, surface membrane depolarization, is rapidly pulsatile. To better understand excitation-transcription coupling we characterized the dependence of cAMP response element-binding protein phosphorylation, a critical step in neuronal plasticity, on the level and duration of membrane depolarization.

L-type calcium channel ligands block nicotine-induced signaling to CREB by inhibiting nicotinic receptors.

Nicotinic acetylcholine receptors (nAChRs) are inhibited by several drugs that are commonly thought to be specific for L-type calcium channels (LTCCs). In neurons, LTCCs are activated by nicotine-induced depolarization to engage downstream signaling events; however, the role of LTCC drug interactions with nAChRs in signaling has not been examined in detail. We investigated the effects of LTCC ligands on nAChR currents and downstream signaling in rat superior cervical ganglion (SCG) neurons.

Weak synaptic activity induces ongoing signaling to the nucleus that is enhanced by BDNF and suppressed by low-levels of nicotine.

The developing nervous system adapts to a wide array of stimuli, in part, by evoking activity-dependent mechanisms that signal to the nucleus and induce long-term modifications in neuronal function. It is well established that one such stimulus is strong synaptic activity. Our interest, however, is whether weak activity generated at developing synapses also signals to the nucleus and if so, can these signals be modulated by extrinsic factors.