JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory.

The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JNK-interacting protein 1 (JIP1) scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the gene that selectively blocks JIP1-mediated JNK activation.

Epileptic pilocarpine-treated rats exhibit aberrant hippocampal EPSP-spike potentiation but retain long-term potentiation.

Hippocampal neuron plasticity is strongly associated with learning, memory, and cognition. In addition to modification of synaptic function and connectivity, the capacity of hippocampal neurons to undergo plasticity involves the ability to change nonsynaptic excitability. This includes altering the probability that EPSPs will generate action potentials (E-S plasticity).

Tone identification behavior in Rattus norvegicus: muscarinic receptor blockage lowers responsiveness in nontarget selective neurons, while nicotinic receptor blockage selectively lowers target responses.

Learning to associate a stimulus with reinforcement causes plasticity in primary sensory cortex. Neural activity caused by the associated stimulus is paired with reinforcement, but population analyses have not found a selective increase in response to that stimulus. Responses to other stimuli increase as much as, or more than, responses to the associated stimulus.

Arc expression and neuroplasticity in primary auditory cortex during initial learning are inversely related to neural activity.

Models of learning-dependent sensory cortex plasticity require local activity and reinforcement. An alternative proposes that neural activity involved in anticipation of a sensory stimulus, or the preparatory set, can direct plasticity so that changes could occur in regions of sensory cortex lacking activity. To test the necessity of target-induced activity for initial sensory learning, we trained rats to detect a low-frequency sound.

Ethanol disrupts NMDA receptor and astroglial EAAT2 modulation of Kv2.1 potassium channels in hippocampus.

Delayed-rectifier Kv2.1 channels are the principal component of voltage-sensitive K+ currents (I(K)) in hippocampal neurons and are critical regulators of somatodendritic excitability. In a recent study, we demonstrated that surface trafficking and phosphorylation of Kv2.

Glutamate transporters regulate extrasynaptic NMDA receptor modulation of Kv2.1 potassium channels.

Delayed-rectifier Kv2.1 potassium channels regulate somatodendritic excitability during periods of repetitive, high-frequency activity. Recent evidence suggests that Kv2.

Retrograde regulation of motoneuron differentiation by muscle beta-catenin.

Synapse formation requires proper interaction between pre- and postsynaptic cells. In anterograde signaling, neurons release factors to guide postsynaptic differentiation. However, less is known about how postsynaptic targets retrogradely regulate presynaptic differentiation or function.

Neuregulin-1 enhances depolarization-induced GABA release.

Neuregulin-1 (NRG1), a regulator of neural development, has been shown to regulate neurotransmission at excitatory synapses. Although ErbB4, a key NRG1 receptor, is expressed in glutamic acid decarboxylase (GAD)-positive neurons, little is known about its role in GABAergic transmission. We show that ErbB4 is localized at GABAergic terminals of the prefrontal cortex.

Adaptive plasticity of NMDA receptors and dendritic spines: implications for enhanced vulnerability of the adolescent brain to alcohol addiction.

It is now known that brain development continues into adolescence and early adulthood and is highly influenced by experience-dependent adaptive plasticity during this time. Behaviorally, this period is also characterized by increased novelty seeking and risk-taking. This heightened plasticity appears to be important in shaping behaviors and cognitive processes that contribute to proper development of an adult phenotype.

Homeostatic plasticity during alcohol exposure promotes enlargement of dendritic spines.

Modifications of the size, shape and number of dendritic spines is thought to be an important component of activity-dependent changes of neuronal circuits, and may play an important role in the plasticity of drug addiction. The present study examined whether homeostatic increases in synaptic N-methyl-d-aspartate (NMDA) receptors in response to chronic ethanol exposure is associated with corresponding morphological changes in dendritic spines. Prolonged exposure of rat hippocampal cultures to either the NMDA receptor antagonist d(-)-2-amino-5-phosphono-pentanoic acid or to ethanol increased punctate staining of F-actin and the postsynaptic density protein-95 (PSD-95).

Structural and functional modifications in glutamateric synapses following prolonged ethanol exposure.

This article summarizes the proceedings of a symposium presented at the 2005 annual meeting of the Research Society on Alcoholism in Santa Barbara, California, USA. The organizer and chair was L. Judson Chandler.

Chronic ethanol induces synaptic but not extrasynaptic targeting of NMDA receptors.

The development of ethanol tolerance and dependence reflects neuroadaptive changes in response to continuous depression in synaptic activity. The present study used confocal imaging and electrophysiology procedures to assess the effects of prolonged ethanol exposure on NMDA receptor trafficking in cultures of hippocampal neurons. Neurons exposed to 50 mm ethanol for 4 d showed an increase in the colocalization of NMDA receptor type 1 (NR1) clusters with the presynaptic marker protein synapsin.