Neuroscience
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Comparative Study
Normal retinal development and retinofugal projections in mice lacking the retina-specific variant of actin-binding LIM domain protein.
The actin-binding LIM domain protein (abLIM) is the mammalian homologue of UNC-115, a protein mediating axon guidance in C. elegans. AbLIM is widely expressed with three isoforms differing from one another by the length of their amino termini. Experiments utilizing dominant-negative mutants in the chick retina suggested a role for abLIM in axon path finding in retinal ganglion cells (RGCs). ⋯ AbLIM-L mutant mice exhibit no apparent morphological or functional defects in photoreceptors and inner retinal neurons. Retinofugal projections and synaptic maturation also appear normal. These data suggest that abLIM-M is likely the isoform performing the essential function related to axon guidance.
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Comparative Study
The differentiation potential of precursor cells from the mouse lateral ganglionic eminence is restricted by in vitro expansion.
We have investigated whether the differentiation potential of attached cultures derived from the mouse lateral ganglionic eminence (LGE) is influenced by in vitro expansion. Primary neuronal cultures derived from the LGE give rise to neurons expressing the striatal projection neuron markers Islet1 (ISL1) and dopamine and cAMP-regulated phosphoprotein of 32 kilodaltons (DARPP-32) as well as the olfactory bulb interneuron marker Er81. Our previous results showed that after expansion in vitro, LGE precursor cells can be induced to differentiate into neurons which exhibit molecular characteristics of the LGE, such as the homeobox transcription factors DLX and MEIS2. ⋯ This indicates that the expansion of LGE precursor cells restricts their differentiation potential in vitro. Interestingly, the undifferentiated LGE cultures retain the expression of both the Isl1 and Er81 genes, suggesting that precursor cells for both striatal projection neurons and olfactory bulb interneurons are present in these cultures. Thus the restriction in differentiation potential of the expanded LGE cultures likely reflects deficiencies in the differentiation conditions used.
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The effects of repeated administration of a tricyclic antidepressant, imipramine, and a selective serotonin reuptake blocker, citalopram, for 14 days (10 mg/kg p.o., twice daily), were studied ex vivo in rat frontal cortex slices prepared 48 h after last dose of the drug. Treatment with both antidepressants resulted in a decrease in the amplitude of field potentials evoked in layer II/III by stimulation of underlying sites in layer V. The amplitude ratio of pharmacologically isolated N-methyl-D-aspartic acid (NMDA) to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components of the field potential was reduced. These results indicate that chronic treatment with imipramine or citalopram results in an attenuation of glutamatergic synaptic transmission in the cerebral cortex.
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Inflammation and reduced forebrain norepinephrine are features of Alzheimer's disease that may interact to contribute to the degeneration of specific neural systems. We reproduced these conditions within the basal forebrain cholinergic system, a region that is vulnerable to degeneration in Alzheimer's disease. Tumor necrosis factor-alpha was infused into the basal forebrain of young mice pretreated with a norepinephrine neuronal toxin, N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP4), with the expectation that the loss of noradrenergic input would enhance the loss of cholinergic neurons. ⋯ Infusion of tumor necrosis factor-alpha into DSP4-pretreated mice also reduced cortical choline acetyltransferase activity on the side of the infusion; however, the decline was not significantly greater than that produced by the infusion of tumor necrosis factor-alpha alone. The neurodegeneration seen may be indirect since a double-immunofluorescence investigation did not find evidence for the co-existence of tumor necrosis factor-alpha type I receptors on choline acetyltransferase-positive cells in the basal forebrain. The results suggest that noradrenergic cell loss in Alzheimer's disease does not augment the consequences of the chronic neuroinflammation and does not enhance neurodegeneration of forebrain cholinergic neurons.
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Latent inhibition describes a process of learning to ignore stimuli of no consequence, and is disrupted in acute, positive-symptomatic schizophrenia. Understanding the neural basis of latent inhibition in animals may help to elucidate the neural dysfunction underlying positive schizophrenic symptoms in man. Evidence suggests a crucial role for dopamine transmission in the nucleus accumbens in the control of latent inhibition. ⋯ In addition to significant non-specific drug effects, a positive control experiment revealed that intra-pallidal picrotoxin significantly enhanced locomotion, suggesting that our manipulations of ventral pallidal GABA function were behaviourally effective. We conclude that modulating ventral pallidal GABA transmission does not affect latent inhibition. The implications of this finding for theories of the neural circuitry mediating latent inhibition and for understanding the functional role of ventral pallidal GABA transmission are discussed.