@article {1684, title = {Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation.}, journal = {Proc Natl Acad Sci U S A}, volume = {114}, year = {2017}, month = {2017 01 24}, pages = {E610-E618}, abstract = {

The signaling mechanisms that choreograph the assembly of the highly asymmetric pre- and postsynaptic structures are still poorly defined. Using synaptosome fractionation, immunostaining, and coimmunoprecipitation, we found that Celsr3 and Vangl2, core components of the planar cell polarity (PCP) pathway, are localized at developing glutamatergic synapses and interact with key synaptic proteins. Pyramidal neurons from the hippocampus of Celsr3 knockout mice exhibit loss of \~{}50\% of glutamatergic synapses, but not inhibitory synapses, in culture. Wnts are known regulators of synapse formation, and our data reveal that Wnt5a inhibits glutamatergic synapses formed via Celsr3. To avoid affecting earlier developmental processes, such as axon guidance, we conditionally knocked out Celsr3 in the hippocampus 1 week after birth. The CA1 neurons that lost Celsr3 also showed a loss of \~{}50\% of glutamatergic synapses in vivo without affecting the inhibitory synapses assessed by miniature excitatory postsynaptic current (mEPSC) and electron microscopy. These animals displayed deficits in hippocampus-dependent behaviors in adulthood, including spatial learning and memory and fear conditioning. In contrast to Celsr3 conditional knockouts, we found that the conditional knockout of Vangl2 in the hippocampus 1 week after birth led to a large increase in synaptic density, as evaluated by mEPSC frequency and spine density. PCP signaling is mediated by multiple core components with antagonizing functions. Our results document the opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation.

}, keywords = {Animals, Behavior, Animal, Cadherins, Cell Polarity, Cells, Cultured, Excitatory Postsynaptic Potentials, Glutamic Acid, Hippocampus, Locomotion, Male, Maze Learning, Mice, Knockout, Nerve Tissue Proteins, Pyramidal Cells, Receptors, Cell Surface, Synapses, Wnt-5a Protein}, issn = {1091-6490}, doi = {10.1073/pnas.1612062114}, author = {Thakar, Sonal and Wang, Liqing and Yu, Ting and Ye, Mao and Onishi, Keisuke and Scott, John and Qi, Jiaxuan and Fernandes, Catarina and Han, Xuemei and Yates, John R and Berg, Darwin K and Zou, Yimin} } @article {139, title = {Neurotransmitter switching in the adult brain regulates behavior.}, journal = {Science}, volume = {340}, year = {2013}, month = {2013 Apr 26}, pages = {449-53}, abstract = {

Neurotransmitters have been thought to be fixed throughout life, but whether sensory stimuli alter behaviorally relevant transmitter expression in the mature brain is unknown. We found that populations of interneurons in the adult rat hypothalamus switched between dopamine and somatostatin expression in response to exposure to short- and long-day photoperiods. Changes in postsynaptic dopamine receptor expression matched changes in presynaptic dopamine, whereas somatostatin receptor expression remained constant. Pharmacological blockade or ablation of these dopaminergic neurons led to anxious and depressed behavior, phenocopying performance after exposure to the long-day photoperiod. Induction of newly dopaminergic neurons through exposure to the short-day photoperiod rescued the behavioral consequences of lesions. Natural stimulation of other sensory modalities may cause changes in transmitter expression that regulate different behaviors.

}, keywords = {Animals, Behavior, Animal, Brain, Cell Count, Dopamine, Dopaminergic Neurons, Hypothalamus, Male, Maze Learning, Photoperiod, Rats, Rats, Long-Evans, Receptors, Dopamine, Receptors, Somatostatin, Seasons, Somatostatin, Stress, Psychological, Synaptic Transmission}, issn = {1095-9203}, doi = {10.1126/science.1234152}, author = {Dulcis, Davide and Jamshidi, Pouya and Leutgeb, Stefan and Spitzer, Nicholas C} } @article {177, title = {Sustained dorsal hippocampal activity is not obligatory for either the maintenance or retrieval of long-term spatial memory.}, journal = {Hippocampus}, volume = {20}, year = {2010}, month = {2010 Dec}, pages = {1366-75}, abstract = {

Memories are initially stored in a labile state and are subject to modification by a variety of treatments, including disruption of hippocampal function. We infused a sodium channel blocker (or CNQX) to inactivate the rat dorsal hippocampus reversibly for 1 week following training on a task of spatial memory (the water maze). Previous work with conventional lesions has established that the dorsal hippocampus is essential for both the acquisition and expression of memory in this task. The question in the present study was whether chronic disruption of neuronal activity in the dorsal hippocampus after training would abolish memory or whether memory would survive extended disruption of hippocampal activity. As expected from earlier work, we found that performance was impaired during the infusion period. The critical test occurred 1 week after the lesion was reversed. We found that retention of the water maze recovered to control levels. Accordingly, sustained hippocampal activity following training is not obligatory for either the maintenance of long-term spatial memory or its subsequent retrieval.

}, keywords = {6-Cyano-7-nitroquinoxaline-2,3-dione, Animals, Excitatory Amino Acid Antagonists, Hippocampus, Male, Maze Learning, Memory, Rats, Rats, Long-Evans, Space Perception, Spatial Behavior}, issn = {1098-1063}, doi = {10.1002/hipo.20722}, author = {Broadbent, Nicola J and Squire, Larry R and Clark, Robert E} }