Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation.

Considerable evidence indicates that the general blockade of protein synthesis prevents both the initial consolidation and the postretrieval reconsolidation of long-term memories. These findings come largely from studies of drugs that block ribosomal function, so as to globally interfere with both cap-dependent and -independent forms of translation. Here we show that intra-amygdala microinfusions of 4EGI-1, a small molecule inhibitor of cap-dependent translation that selectively disrupts the interaction between eukaryotic initiation factors (eIF) 4E and 4G, attenuates fear memory consolidation but not reconsolidation. Using a combination of behavioral and biochemical techniques, we provide both in vitro and in vivo evidence that the eIF4E-eIF4G complex is more stringently required for plasticity induced by initial learning than for that triggered by reactivation of an existing memory.

Multiple components of eIF4F are required for protein synthesis-dependent hippocampal long-term potentiation.

Persistent forms of synaptic plasticity are widely thought to require the synthesis of new proteins. This feature of long-lasting forms of plasticity largely has been demonstrated using inhibitors of general protein synthesis, such as either anisomycin or emetine. However, these drugs, which inhibit elongation, cannot address detailed questions about the regulation of translation initiation, where the majority of translational control occurs. Moreover, general protein synthesis inhibitors cannot distinguish between cap-dependent and cap-independent modes of translation initiation. In the present study, we took advantage of two novel compounds, 4EGI-1 and hippuristanol, each of which targets a different component of the eukaryotic initiation factor (eIF)4F initiation complex, and investigated their effects on long-term potentiation (LTP) at CA3-CA1 synapses in the hippocampus. We found that 4EGI-1 and hippuristanol both attenuated long-lasting late-phase LTP induced by two different stimulation paradigms. We also found that 4EGI-1 and hippuristanol each were capable of blocking the expression of newly synthesized proteins immediately after the induction of late-phase LTP. These new pharmacological tools allow for a more precise dissection of the role played by translational control pathways in synaptic plasticity and demonstrate the importance of multiple aspects of eIF4F in processes underlying hippocampal LTP, laying the foundation for future studies investigating the role of eIF4F in hippocampus-dependent memory processes.

Epilepsy-Induced Reduction in HCN Channel Expression Contributes to an Increased Excitability in Dorsal, But Not Ventral, Hippocampal CA1 Neurons.

CA1 neurons in epileptic animals are vulnerable to selective changes in ion channel expression, called acquired channelopathies, which can increase the excitability of a neuron. Under normal conditions there is a gradient of ion channel expression and intrinsic excitability along the longitudinal, dorsoventral axis of hippocampal area CA1 of the rodent. Many of these channels, including M-channels, GIRK channels and HCN channels, all have dorsoventral expression gradients that might be altered in rodent models of epilepsy. Here, we show that the excitability of dorsal, but not ventral CA1 neurons, had an increased firing rate, reduced interspike interval (ISI) and increased input resistance in a status epilepticus (SE) model of temporal lobe epilepsy (TLE). As a result, the excitability of CA1 neurons became uniform across the dorsoventral axis of the rat hippocampus post-SE. Using current clamp recordings with pharmacology and immunohistochemistry, we demonstrate that the expression of HCN channels was downregulated in the dorsal CA1 region post-SE, while the expression of M and GIRK channels were unchanged. We did not find this acquired channelopathy in ventral CA1 neurons post-SE. Our results suggest that the excitability of dorsal CA1 neurons post-SE increase to resemble the intrinsic properties of ventral CA1 neurons, which likely makes the hippocampal circuit more permissible to seizures, and contributes to the cognitive impairments associated with chronic epilepsy.

The development of health care-seeking behaviors in traditional-age undergraduate college students.

PURPOSE: Traditional-age undergraduate college students are embarking into the world of autonomous decision making. These decisions encompass not only academics but also lifestyle and life-skills. One of the life-skill areas in which students have difficulty is seeking health care independently. The aim of this pilot study is to gather qualitative data to help illuminate the process of the development of health care-seeking behaviors in traditional-age undergraduate college students (18-23 years). DATA SOURCE: A purposive focus group sample of eight traditional-age undergraduate college students was recruited from a private university in the northeastern United States. CONCLUSIONS: Five major themes emerged: needing help or care, expectations, decision making, healthcare accessibility, and future needs. Health care for these student participants is expected upon demand by them in this "age of convenience." IMPLICATIONS FOR PRACTICE: The findings indicate these traditional-age undergraduate college students view themselves as independent but still rely on parental supervision of health care. Implications for providing primary health care for this generation may include marketing strategies to meet this perspective of "24-7" care based upon this limited focus group, but further expanded studies are needed for generalizations.