Glutamatergic Pyramidal Neurons Research Articles

Fibroblast Growth Factor 2 Is Necessary for the Growth of Glutamate Projection Neurons in the Anterior Neocortex

Basic fibroblast growth factor (Fgf2) is required for the generation of founder cells within the dorsal pseudostratified ventricular epithelium, which will generate the cerebral cortex, but the ganglionic eminences are not affected. We report here that the Fgf2 null mutant mice show an approximately 40% decrease in cortical glutamatergic pyramidal neurons. In contrast, no change in pyramidal or granule cell number is detected in the hippocampus of Fgf2 -/- mice. In addition, the soma of the pyramidal cells in the frontal and parietal cortices are smaller in Fgf2 knock-out mice. The decrease in the number and size of glutamatergic neuronal population affects all cortical layers but is restricted to the frontal and parietal cortices without any change in the occipital cortex, indicating that Fgf2 is necessary to regulate cell number and size in the anterior cerebral cortex. In contrast to pyramidal neurons, cortical GABA interneurons are unaffected by the lack of Fgf2. The resulting imbalance between the excitatory and inhibitory neurotransmission in the cerebral cortex is reflected by an increased duration of sleep when the animals receive a GABA receptor agonist. Thus, Fgf2 signaling may contribute to the regional specification of the cerebral cortex and may play a role in increasing the size of anterior cortical regions during vertebrate evolution.

Dynamic localization and clustering of dendritic Kv2.1 voltage-dependent potassium channels in developing hippocampal neurons

Dendritic excitability is modulated by the highly variable spatial and temporal expression pattern of voltage-dependent potassium channels. Somatodendritic Kv2.1 channels contribute a major component of delayed rectifier potassium current in cultured hippocampal neurons, where Kv2.1 is localized to large clusters on the soma and proximal dendrites. Here we found that dramatic differences exist in the clustering of endogenous Kv2.1 in cultured rat hippocampal GABAergic interneurons and glutamatergic pyramidal neurons. Studies on neurons developing in culture revealed that while a similar sequence of Kv2.1 localization and clustering occurred in both cell types, the process was temporally delayed in pyramidal cells. Localization and clustering of recombinant green fluorescent protein-tagged Kv2.1 occurred by the same sequence of events, and imaging of GFP–Kv2.1 clustering in living neurons revealed dynamic fusion events that underlie cluster formation. Overexpression of GFP–Kv2.1 accelerated the clustering program in pyramidal neurons such that the observed differences in Kv2.1 clustering in pyramidal neurons and interneurons were eliminated. Confocal imaging showed a preferential association of Kv2.1 with the basal membrane in cultured neurons, and electrophysiological recordings from neurons cultured on transistors revealed that Kv2.1 contributed the bulk of a previously described adherens junction delayed rectifier potassium conductance. Finally, Kv2.1 clusters were found spatially associated with ryanodine receptor intracellular Ca 2+ ([Ca 2+] i) release channels. These findings reveal a stepwise assembly of Kv2.1 potassium channels into membrane clusters during development, and an association of these clusters with Ca 2+ signaling apparatus. Together these data suggest that the restricted localization of Kv2.1 may play an important role in the previously observed contribution of this potassium channel in regulating dendritic [Ca 2+] i transients.

A long, remarkable journey: tangential migration in the telencephalon.

Recent studies on the origin of cell populations in rodent and chicken embryonic brains provide evidence for extensive tangential migration within the developing telencephalon. On the basis of these findings, a new concept of corticogenesis has emerged, which proposes that two distinct neuronal populations cooperate in the formation of the cortex. One population consists of radially migrating neurons that originate in the ventricular zone of the pallium (cortex) and give rise to the glutamatergic pyramidal neurons. The second population consists of tangentially migrating neurons that originate in the ventricular zone of the subpallium (subcortical telencephalon) and give rise to GABA (γ-aminobutyric acid)-producing local circuit neurons. The subpallium is also the origin of other cell types that follow distinct tangential trajectories to migrate to structures such as the olfactory bulb and the striatum. Here, we review evidence that supports the existence of several tangential migration pathways in the telencephalon, and summarize recent findings that describe their regulation.

Distribution of N-acetylaspartylglutamate immunoreactivity in human brain and its alteration in neurodegenerative disease

The dipeptide N-acetylaspartylglutamate (NAAG) may be involved in the process of glutamatergic signaling by both acting at glutamate receptors and as a glutamate protransmitter. In the present study we determined the cellular localization and distribution of NAAG-like immunoreactivity (NAAG-LI) in normal human brain and in neurodegenerative disorders to ascertain the degree of NAAG's colocalization to putative glutamatergic pathways. Immunohistochemistry with an antibody against NAAG was performed on control, Huntington's disease (HD) and Alzheimer's disease (AD) human autopsy and biopsy brain sections from the cerebral cortex, hippocampus, amygdala, neostriatum, brainstem and spinal cord. In normal human brain, NAAG-LI was widespread localized to putative glutamatergic pyramidal neurons of the cerebral cortex and hippocampus. Punctate NAAG-LI was present in areas known to receive neuronal glutamatergic input, such as layer IV of the cerebral cortex, striatal neuropil, and the outer portion of the molecular layer of the hippocampal dentate gyrus. In the two pathologic brain regions examined, the HD neostriatum and the AD temporal cortex, we observed a widespread loss of NAAG-LI neurons. In addition NAAG-LI reactive microglia surrounding plaques were seen in AD temporal cortex but not in the HD striatum. Our results suggest that NAAG is substantially localized to putative glutamatergic pathways in human brain and that NAAG-LI neurons are vulnerable to the neurodegenerative process in HD and AD.

Cholinergic terminals in the cat visual cortex: ultrastructural basis for interaction with glutamate-immunoreactive neurons and other cells.

Acetylcholine (ACh) is one of the transmitters utilized by extra-thalamic afferents to modulate stimulus-driven neurotransmission and experience-dependent plasticity in the visual cortex. Since these processes also depend on the activation of glutamatergic receptors, cholinergic terminals may exert their effects via direct modulation of excitatory neurotransmission. The objective of this study was to determine whether the ultrastructural relationships between cholinergic terminals, glutamate-immunoreactive neurons, and other unlabeled cells support this idea. Sections from aldehyde-fixed visual cortex (area 17) of adult cats were immunolabeled for the following molecules: (1) choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme; (2) L-glutamate; or (3) ChAT simultaneously with L-glutamate by combining electron-microscopic immunogold and immunoperoxidase techniques. None of the cortical terminals were dually labeled, suggesting that (1) the labeling procedure was free of chemical or immunological cross reactions; and (2) glutamate immunoreactivity probably reflects the transmitter, and not metabolic, pool of L-glutamate. Comparisons between cholinergic and noncholinergic axons revealed that (1) ChAT-immunoreactive axons formed fewer identifiable synaptic contacts within single ultrathin sections (P less than 0.01 using chi-square test); and (2) more of the cholinergic axons occurred directly opposed to other terminals (P less than 0.0015 by chi-square test), including 21% of which resided directly across asymmetric, axo-spinous junctions. Dual labeling showed that a third of the synaptic targets for cholinergic terminals contained detectable levels of glutamate immunoreactivity. Some of the axo-spinous junctions juxtaposed to cholinergic axons also exhibited glutamate immunoreactivity presynaptically. These observations provide ultrastructural evidence for direct, cholinergic modulation of glutamatergic pyramidal neurons within the mammalian neocortex. Prevalence of juxtapositions between cholinergic terminals and axo-spinous synapses supports the following ideas: (1) ACh may modulate the release of noncholinergic transmitters, including Glu; (2) Glu may modulate ACh release; and (3) these processes may be concurrent with cholinergic modulation of glutamatergic synapses at postsynaptic sites.