Ultrastructural localization of dynorphin in the dentate gyrus in human temporal lobe epilepsy: A study of reorganized mossy fiber synapses

Zhang, Nianhui; Houser, Carolyn R.

doi:10.1002/(sici)1096-9861(19990322)405:4<472::aid-cne3>3.0.co;2-p

Cited by 81 publications

(51 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mossy fiber sprouting is also observed in epilepsy patients (49–51). SE can induce aberrant sprouting of mossy fibers accompanied by new synaptic connections with both excitatory granule cells and inhibitory interneurons (52–55). Whereas some studies have reported that synaptic reorganization of mossy fibers creates new recurrent excitatory circuits (56, 57), others have shown that reorganization can lead to greater inhibition in the dentate gyrus when sprouting occurs (58).…”

Section: Potential Epileptogenic Processesmentioning

confidence: 99%

Candidate Drug Targets for Prevention or Modification of Epilepsy

Varvel

Jiang²,

Dingledine³

2015

Annu. Rev. Pharmacol. Toxicol.

View full text Add to dashboard Cite

Epilepsy is a prevalent neurological disorder afflicting nearly 50 million people worldwide. The disorder is characterized clinically by recurrent spontaneous seizures attributed to abnormal synchrony of brain neurons. Despite advances in the treatment of epilepsy, nearly one-third of patients are resistant to current therapies, and the underlying mechanisms whereby a healthy brain becomes epileptic remain unresolved. Therefore, researchers have a major impetus to identify and exploit new drug targets. Here we distinguish between epileptic effectors, or proteins that set the seizure threshold, and epileptogenic mediators, which control the expression or functional state of the effector proteins. Under this framework, we then discuss attempts to regulate the mediators to control epilepsy. Further insights into the complex processes that render the brain susceptible to seizures and the identification of novel mediators of these processes will lead the way to the development of drugs to modify disease outcome and, potentially, to prevent epileptogenesis.

show abstract

Section: Potential Epileptogenic Processesmentioning

confidence: 99%

Candidate Drug Targets for Prevention or Modification of Epilepsy

Varvel

Jiang²,

Dingledine³

2015

Annu. Rev. Pharmacol. Toxicol.

View full text Add to dashboard Cite

show abstract

“…In many patients with temporal lobe epilepsy (Sutula et al, 1989; de Lanerolle et al, 1989; Houser et al, 1990) and after epileptogenic injuries in animal models (Nadler et al, 1980; Lemos and Cavalheiro, 1995; Golarai et al, 2001; Santhakumar et al, 2001) granule cell axons (mossy fibers) grow from their normal location in the hilus into the molecular layer where they form synapses (Babb et al, 1991; Represa et al, 1993; Zhang and Houser, 1999; Buckmaster et al, 2002) and excite neighboring granule cells (Wuarin and Dudek, 1996; Molnár and Nadler, 1999; Lynch and Sutula, 2000; Scharfman et al, 2003). Some studies found positive correlations between anatomical measures of mossy fiber sprouting and seizure frequency (Mathern et al, 1993, 1997; Lemos and Cavalheiro, 1995; Wenzel et al, 2000b; Pitkänen et al, 2005; Kharatishvili et al, 2006), but most have not (Cronin and Dudek, 1988; Sloviter, 1992; Masukawa et al, 1992; Mello et al, 1993; Buckmaster and Dudek, 1997; Spencer et al, 1999; Timofeeva and Peterson, 1999; Gorter et al, 2001; Nissinen et al, 2001; Lynd-Balta et al, 2004; Rao et al, 2006; Pitkänen et al, 2000; Wenzel et al, 2000a; Lehmann et al, 2001; Zhang et al, 2002; Raol et al, 2003; Jung et al, 2004; Williams et al, 2004; Harvey and Sloviter, 2005; Kadam and Dudek, 2007; Buckmaster and Lew, 2011).…”

Section: Introductionmentioning

confidence: 99%

Increased Excitatory Synaptic Input to Granule Cells from Hilar and CA3 Regions in a Rat Model of Temporal Lobe Epilepsy

Zhang¹,

Huguenard²,

Buckmaster³

2012

J. Neurosci.

View full text Add to dashboard Cite

One potential mechanism of temporal lobe epilepsy is recurrent excitation of dentate granule cells through aberrant sprouting of their axons (mossy fibers), which is found in many patients and animal models. However, correlations between the extent of mossy fiber sprouting and seizure frequency are weak. Additional potential sources of granule cell recurrent excitation that would not have been detected by markers of mossy fiber sprouting in previous studies include surviving mossy cells and proximal CA3 pyramidal cells. To test those possibilities in hippocampal slices from epileptic pilocarpine-treated rats, laser scanning glutamate uncaging was used to randomly and focally activate neurons in the granule cell layer, hilus, and proximal CA3 pyramidal cell layer while measuring evoked excitatory postsynaptic currents (EPSCs) in normotopic granule cells. Consistent with mossy fiber sprouting, a higher proportion of glutamate-uncaging spots in the granule cell layer evoked EPSCs in epileptic rats compared to controls. In addition, stimulation spots in the hilus and proximal CA3 pyramidal cell layer were more likely to evoke EPSCs in epileptic rats, despite significant neuron loss in those regions. Furthermore, synaptic strength of recurrent excitatory inputs to granule cells from CA3 pyramidal cells and other granule cells was increased in epileptic rats. These findings reveal substantial levels of excessive, recurrent, excitatory synaptic input to granule cells from neurons in the hilus and proximal CA3 field. The aberrant development of these additional positive-feedback circuits might contribute to epileptogenesis in temporal lobe epilepsy.

show abstract

“…In human temporal lobe epilepsy, one characteristic change is the extensive remodeling of mossy fibers and terminals in the hippocampus, notably with abnormal innervation of the inner molecular layer of the dentate gyrus (Sutula et al 1989; Babb et al 1991). The enlarged sprouting mossy fibers form synaptic contacts in this latter area with numerous enlarged, complex, and often invaginating spines that overall resemble the thorny excrescences of mossy terminal synapses of the CA3 and CA4 seen in normal animals (Zhang and Houser 1999). This suggests that for synapses in the hippocampus at least, spine invagination is induced by mossy terminal formation (Zhao et al 2012; see also Nek et al 1993).…”

Section: Pathology Of Invaginating and Other Spine Synapsesmentioning

confidence: 92%

“…This suggests that for synapses in the hippocampus at least, spine invagination is induced by mossy terminal formation (Zhao et al 2012; see also Nek et al 1993). Related to this idea, Zhang and Houser (1999) discuss how the formation of the complex, excrescence-like spines (with perforated densities, spinules, invaginating spine processes, and more organelles) indicate synaptic plasticity leading to greater synaptic efficacy. The abnormal formation of these mossy terminal synapses in the molecular layer of the dentate gyrus may contribute to the hyperexcitability that is seen in granule cells of the dentate gyrus in epilepsy.…”

Section: Pathology Of Invaginating and Other Spine Synapsesmentioning

confidence: 99%

The Diversity of Spine Synapses in Animals

et al. 2016

View full text Add to dashboard Cite

Here we examine the structure of the various types of spine synapses throughout the animal kingdom. Based on available evidence, we suggest that there are two major categories of spine synapses: invaginating and non-invaginating, with distributions that vary among different groups of animals. In the simplest living animals with definitive nerve cells and synapses, the cnidarians and ctenophores, most chemical synapses do not form spine synapses. But some cnidarians have invaginating spine synapses, especially in photoreceptor terminals of motile cnidarians with highly complex visual organs, and also in some mainly sessile cnidarians with rapid prey capture reflexes. This association of invaginating spine synapses with complex sensory inputs is retained in the evolution of higher animals in photoreceptor terminals and some mechanoreceptor synapses. In contrast to invaginating spine synapse, non-invaginating spine synapses have been described only in animals with bilateral symmetry, heads and brains, associated with greater complexity in neural connections. This is apparent already in the simplest bilaterians, the flatworms, which can have well-developed non-invaginating spine synapses in some cases. Non-invaginating spine synapses diversify in higher animal groups. We also discuss the functional advantages of having synapses on spines and more specifically, on invaginating spines. And finally we discuss pathologies associated with spine synapses, concentrating on those systems and diseases where invaginating spine synapses are involved.

show abstract

Ultrastructural localization of dynorphin in the dentate gyrus in human temporal lobe epilepsy: A study of reorganized mossy fiber synapses

Cited by 81 publications

References 92 publications

Candidate Drug Targets for Prevention or Modification of Epilepsy

Candidate Drug Targets for Prevention or Modification of Epilepsy

Increased Excitatory Synaptic Input to Granule Cells from Hilar and CA3 Regions in a Rat Model of Temporal Lobe Epilepsy

The Diversity of Spine Synapses in Animals

Contact Info

Product

Resources

About