Age-related cognitive impairments in mice with a conditional ablation of the neural cell adhesion molecule.

Most of the mechanisms involved in neural plasticity support cognition, and aging has a considerable effect on some of these processes. The neural cell adhesion molecule (NCAM) of the immunoglobulin superfamily plays a pivotal role in structural and functional plasticity and is required to modulate cognitive and emotional behaviors. However, whether aging is associated with NCAM alterations that might contribute to age-related cognitive decline is not currently known.

SAP97 directs NMDA receptor spine targeting and synaptic plasticity.

SAP97 is a multidomain scaffold protein implicated in the forward trafficking and synaptic localization of NMDA- and AMPA-type glutamate receptors. Alternative splicing of SAP97 transcripts gives rise to palmitoylated αSAP97 and L27-domain containing βSAP97 isoforms that differentially regulate the subsynaptic localization of GluR1 subunits of AMPA receptors. Here, we examined whether SAP97 isoforms regulate the mechanisms underlying long-term potentiation (LTP) and depression (LTD) and find that both α- and β-forms of SAP97 impair LTP but enhance LTD via independent isoform-specific mechanisms.

Intra-spaced stimulation and protein phosphatase 1 dictate the direction of synaptic plasticity.

Changes in the strength of synapses in the hippocampus that occur with long-term potentiation (LTP) or long-term depression (LTD) are thought to underlie the cellular basis of learning and memory. Memory formation is known to be regulated by spacing intervals between training episodes. Using paired whole-cell recordings to record from synapses connecting two CA3 pyramidal neurons, we now show that stimulation frequency and spacing between LTP and LTD induction protocols alter the expression of synaptic plasticity.

Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons.

The physiological contribution of glucose in thermoregulation is not completely established nor whether this control may involve a regulation of the melanocortin pathway. Here, we assessed thermoregulation and leptin sensitivity of hypothalamic arcuate neurons in mice with inactivation of glucose transporter type 2 (Glut2)-dependent glucose sensing. Mice with inactivation of Glut2-dependent glucose sensors are cold intolerant and show increased susceptibility to food deprivation-induced torpor and abnormal hypothermic response to intracerebroventricular administration of 2-deoxy-d-glucose compared to control mice.

Synaptic SAP97 isoforms regulate AMPA receptor dynamics and access to presynaptic glutamate.

The synaptic insertion of GluR1-containing AMPA-type glutamate receptors (AMPARs) is critical for synaptic plasticity. However, mechanisms responsible for GluR1 insertion and retention at the synapse are unclear. The synapse-associated protein SAP97 directly binds GluR1 and participates in its forward trafficking from the Golgi network to the plasma membrane.

Control of the establishment of aversive memory by calcineurin and Zif268.

Emotional memory is a rapidly acquired and persistent form of memory, and its robustness is in part determined by the initial strength of the memory. Here, we provide new evidence that the protein phosphatase calcineurin (CaN), a potent negative regulator of neuronal signaling that is known to constrain learning and memory, critically regulates the establishment of emotional memory through mechanisms involving the immediate early gene Zif268 (also known as Egr1). We found that CaN is inhibited in the amygdala during the establishment of aversive memory, but Zif268 is activated.

Glutamate receptor plasticity at excitatory synapses in the brain.

1. Synapse plasticity, defined as an activity dependent change in the strength of synapses, was first described in 1973 and, since those seminal experiments were reported, the field of synapse plasticity has expanded into one of the most widely studied areas in neuroscience. 2.

Protein phosphatase 1 is a molecular constraint on learning and memory.

Repetition in learning is a prerequisite for the formation of accurate and long-lasting memory. Practice is most effective when widely distributed over time, rather than when closely spaced or massed. But even after efficient learning, most memories dissipate with time unless frequently used.