An abnormal GABAergic system in the inferior colliculus provides a basis for audiogenic seizures in genetically epilepsy-prone rats.

In this review of neuroanatomical studies of the genetically epilepsy-prone rat (GEPR), three main topics will be covered. First, the number of GABAergic neurons and total neurons in the inferior colliculus of GEPRs will be compared to those of the nonepileptic Sprague-Dawley rat. Next, the number of small neurons in the inferior colliculus will be described in both developmental and genetic analyses of GEPRs and their backcrosses.

Synaptic connections of hilar basal dendrites of dentate granule cells in a neonatal hypoxia model of epilepsy.

Numerous animal models of epileptogenesis demonstrate neuroplastic changes in the hippocampus. These changes occur not only for the mature neurons and glia, but also for the newly generated granule cells in the dentate gyrus. One of these changes, the sprouting of mossy fiber axons, is derived predominantly from newborn granule cells in adult rats with pilocarpine-induced temporal lobe epilepsy.

Astrocyte Alterations in the Hippocampus Following Pilocarpine-induced Seizures in Aged Rats.

It is known that the incidence of epilepsy increases with age, but only a few studies have investigated the consequences and mechanisms of seizure and epilepsy in aged animals. Astrocytic changes are known to directly influence neuronal excitability and seizure susceptibility. However, information regarding alterations to astrocytes after seizures in aged animals is lacking in the literature.

Seizure-induced Increased Neurogenesis Occurs in the Dentate Gyrus of Aged Sprague-Dawley Rats.

Neurogenesis in the hippocampal dentate gyrus persists throughout the lifespan of mammals, however, the rate of neurogenesis decreases as the animal ages. Although seizures increase neurogenesis in young adult brains, this relationship has not been shown in aged animals. Using doublecortin (DCX) immunocytochemistry, the number of DCX-labeled cells in the dentate gyrus from aged rats (23 months of age) was assessed 30 days following pilocarpine-induced seizures and was compared to the number obtained from age-matched control rats.

Microglia-associated granule cell death in the normal adult dentate gyrus.

Microglial cells are constantly monitoring the central nervous system for sick or dying cells and pathogens. Previous studies showed that the microglial cells in the dentate gyrus have a heterogeneous morphology with multipolar cells in the hilus and fusiform cells apposed to the granule cell layer both at the hilar and at the molecular layer borders. Although previous studies showed that the microglia in the dentate gyrus were not activated, the data in the present study show dying granule cells apposed by Iba1-immunolabeled microglial cell bodies and their processes both at hilar and at molecular layer borders of the granule cell layer.

Dentate granule cells form hilar basal dendrites in a rat model of hypoxia-ischemia.

Hilar basal dendrites form on dentate granule cells following seizures. To determine whether other brain insults cause the formation of hilar basal dendrites, a model of global cerebral hypoxia/ischemia was used. Rats underwent a transient induction of ischemia by occlusion of both common carotid arteries followed by reperfusion.

Long-term survival of olfactory sensory neurons after target depletion.

Life-long addition and elimination of neurons within the adult olfactory epithelium and olfactory bulb allows for adaptive structural responses to sensory experience, learning, and recovery after injury. The interdependence of the two structures is highlighted by the shortened life span of sensory neurons deprived of bulb contact, and has prompted the hypothesis that trophic cues from the bulb contribute to their survival. The specific identity and source of these signals remain unknown.

Proximity of excitatory and inhibitory axon terminals adjacent to pyramidal cell bodies provides a putative basis for nonsynaptic interactions.

Although pyramidal cells are the main excitatory neurons in the cerebral cortex, it has recently been reported that they can evoke inhibitory postsynaptic currents in neighboring pyramidal neurons. These inhibitory effects were proposed to be mediated by putative axo-axonic excitatory synapses between the axon terminals of pyramidal cells and perisomatic inhibitory axon terminals [Ren M, Yoshimura Y, Takada N, Horibe S, Komatsu Y (2007) Science 316:758-761]. However, the existence of this type of axo-axonic synapse was not found using serial section electron microscopy.

Morphological and ultrastructural features of Iba1-immunolabeled microglial cells in the hippocampal dentate gyrus.

Microglia are found throughout the central nervous system, respond rapidly to pathology and are involved in several components of the neuroinflammatory response. Iba1 is a marker for microglial cells and previous immunocytochemical studies have utilized this and other microglial-specific antibodies to demonstrate the morphological features of microglial cells at the light microscopic level. However, there is a paucity of studies that have used microglial-specific antibodies to describe the ultrastructural features of microglial cells and their processes.

Subventricular zone-derived, newly generated neurons populate several olfactory and limbic forebrain regions.

Neurogenesis persists in several regions of the adult mammalian brain. Although the hippocampus and olfactory bulb are most commonly studied in the context of adult neurogenesis, there is an increasing body of evidence in support of neurogenesis occurring outside of these two regions. The current study expands on previous data by showing newborn neurons with a mature phenotype are located in several olfactory and limbic structures outside of the hippocampus and olfactory bulb, where we previously described doublecortin/bromodeoxyuridine immature neurons.

Structural changes for adult-born dentate granule cells after status epilepticus.

Status epilepticus (SE) not only results in an increased number of newly generated neurons in the dentate gyrus but also leads to structural alterations of many of these newborn granule cells. One of the structural changes involving newly generated dentate granule cells is the formation of hilar basal dendrites that persist on mature granule cells and integrate into synaptic circuitry. SE also causes other newborn granule cells to migrate ectopically into the hilus, and these cells also integrate into synaptic circuitry.

Neurons born in the adult dentate gyrus form functional synapses with target cells.

Adult neurogenesis occurs in the hippocampus and the olfactory bulb of the mammalian CNS. Recent studies have demonstrated that newborn granule cells of the adult hippocampus are postsynaptic targets of excitatory and inhibitory neurons, but evidence of synapse formation by the axons of these cells is still lacking. By combining retroviral expression of green fluorescent protein in adult-born neurons of the mouse dentate gyrus with immuno-electron microscopy, we found output synapses that were formed by labeled terminals on appropriate target cells in the CA3 area and the hilus.

Synaptic input to dentate granule cell basal dendrites in a rat model of temporal lobe epilepsy.

In patients with temporal lobe epilepsy some dentate granule cells develop basal dendrites. The extent of excitatory synaptic input to basal dendrites is unclear, nor is it known whether basal dendrites receive inhibitory synapses. We used biocytin to intracellularly label individual granule cells with basal dendrites in epileptic pilocarpine-treated rats.

In DRG11 knock-out mice, trigeminal cell death is extensive and does not account for failed brainstem patterning.

A previous study (Ding et al., 2003) showed that the homeodomain transcription factor DRG11 is necessary for pattern formation in the trigeminal nucleus principalis (PrV), the requisite brainstem nucleus for development of the whisker-to-barrel cortex pathway. However, it is not known how DRG11 contributes to pattern formation.

Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats.

Astrocyte and microglial activation occurs following seizures and plays a role in epileptogenesis. However, the precise temporal and spatial response to seizures has not been fully examined. The pilocarpine model of temporal lobe epilepsy was selected to examine glial changes following seizures because morphological changes in the hippocampus closely mimic the human condition.

Ultrastructure and synaptic connectivity of cell types in the adult rat dentate gyrus.

The rat hippocampal dentate gyrus is an extensively studied structural component of the limbic system. It is the first station in the classical tri-synaptic circuit of the hippocampus in that its major input arises from the entorhinal cortex via the perforant pathway. The second part of this circuit arises from the projection cells of the dentate gyrus, the granule cells, which send their axons to the pyramidal cells of CA3.

Origin, migration and fate of newly generated neurons in the adult rodent piriform cortex.

Newly generated neurons are continuously added to the olfactory epithelium and olfactory bulbs of adult mammals. Studies also report newly generated neurons in the piriform cortex, the primary cortical projection site of the olfactory bulbs. The current study used BrdU-injection paradigms, and in vivo and in vitro DiI tracing methods to address three fundamental issues of these cells: their origin, migratory route and fate.

Newly generated granule cells show rapid neuroplastic changes in the adult rat dentate gyrus during the first five days following pilocarpine-induced seizures.

Long-term neuroplastic changes to dentate granule cells have been reported after seizures and were shown to contribute to recurrent excitatory circuitry. These changes include increased numbers of newborn granule cells, sprouted mossy fibers, granule cell layer dispersion, increased hilar ectopic granule cells and formation of hilar basal dendrites on granule cells. The goal of the current study was to determine the acute progression of neuroplastic changes involving newly generated granule cells after pilocarpine-induced seizures.

Olfactory enrichment enhances the survival of newly born cortical neurons in adult mice.

Neurogenesis persists in the adult rodent olfactory epithelium and olfactory bulbs. Recent studies suggest that neurogenesis might also occur in the adult rodent piriform cortex, the primary cortical projection site of the olfactory bulbs. To determine whether olfactory enrichment influences neurogenesis in the mouse piriform cortex, olfactory enrichment was used in combination with bromodeoxyuridine labeling.

Dendritic development of newly generated neurons in the adult brain.

Ramon y Cajal described the fundamental morphology of the dendritic and axonal growth cones of neurons during development. However, technical limitations at the time prevented him from describing such growth cones from newborn neurons in the adult brain. The phenomenon of adult neurogenesis is briefly reviewed, and the structural description of dendritic and axonal outgrowth for these newly generated neurons in the adult brain is discussed.

Spatiotemporal profile of dendritic outgrowth from newly born granule cells in the adult rat dentate gyrus.

Neurogenesis in the adult dentate gyrus occurs in the subgranular zone where newborn neurons (NNs) migrate a short distance into the granule cell layer and extend their rudimentary apical dendritic processes upon a radial glial scaffold. Using doublecortin (DCX) immunocytochemistry, these growing dendrites can be visualized because dendritic growth cones, including filipodia and lamellipodia, are labeled in both light and electron microscopic preparations. To study the rate of dendritic outgrowth of newborn dentate granule cells, single injections of 5-bromo-2-deoxyuridine (BrdU) with different survival times were combined with double immunolabeling for BrdU and DCX.

Newly born dentate granule neurons after pilocarpine-induced epilepsy have hilar basal dendrites with immature synapses.

Neurogenesis in the subgranular zone of the dentate gyrus persists throughout the lifespan of mammals, and the resulting newly born neurons are incorporated into existing hippocampal circuitry. Seizures increase the rate of neurogenesis in the adult rodent brain and result in granule cells in the dentate gyrus with basal dendrites. Using doublecortin (DCX) immunocytochemistry to label newly generated neurons the current study focuses on the electron microscopic features of DCX-labeled cell bodies and dendritic processes in the dentate gyrus of rats with pilocarpine-induced epilepsy.