Rapid Deletion of Mossy Cells Does Not Result in a Hyperexcitable Dentate Gyrus: Implications for Epileptogenesis

Ratzliff, Anna; Howard, Allyson; Santhakumar, Vijayalakshmi; Osapay, Imola; Soltész, Iván

doi:10.1523/jneurosci.5191-03.2004

Cited by 109 publications

(107 citation statements)

References 55 publications

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“…Hyperexcitability of the hippocampal dentate gyrus has been described in the popular lateral fluid percussion injury model of closed head injury in the rat and potentially attributed to alterations in hippocampal circuitry (Lowenstein et al, 1992;Coulter et al, 1996;Toth et al, 1997;Santhakumar et al, 2000Santhakumar et al, , 2001. Cytoarchitectual changes as demonstrated by selective hilar neuronal loss (Lowenstein et al, 1992;Toth et al, 1997;Santhakumar et al, 2000Santhakumar et al, , 2001 and mossy fiber sprouting (Santhakumar et al, 2001) have been shown and associated with dentate granule cell hyperexcitability, although some recent studies refute this hypothesis (Ratzliff et al, 2004). Larger, longer-lasting multiphasic field potential have been recorded from the hippocampus of animals after TBI compared to field potentials in controls (Santhakumar et al, 2000(Santhakumar et al, , 2001Akasu et al, 2002;Coulter et al, 2002).…”

Section: Traumatic Brain Injury-induced Spontaneous Recurrent Seizuresmentioning

confidence: 99%

Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy

DeLorenzo

Sun

Deshpande

2005

Pharmacology & Therapeutics

260

286

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Epilepsy is one of the most common neurological disorders. Although epilepsy can be idiopathic, it is estimated that up to 50% of all epilepsy cases are initiated by neurological insults and are called acquired epilepsy (AE). AE develops in 3 phases: (1) the injury (central nervous system [CNS] insult), (2) epileptogenesis (latency), and (3) the chronic epileptic (spontaneous recurrent seizure) phases. Status epilepticus (SE), stroke, and traumatic brain injury (TBI) are 3 major examples of common brain injuries that can lead to the development of AE. It is especially important to understand the molecular mechanisms that cause AE because it may lead to innovative strategies to prevent or cure this common condition. Recent studies have offered new insights into the cause of AE and indicate that injury-induced alterations in intracellular calcium concentration levels [Ca 2+ ] i and calcium homeostatic mechanisms play a role in the development and maintenance of AE. The injuries that cause AE are different, but they share a common molecular mechanism for producing brain damage -an increase in extracellular glutamate concentration that causes increased intracellular neuronal calcium, leading to neuronal injury and/or death. Neurons that survive the injury induced by glutamate and are exposed to increased [Ca 2+ ] i are the cellular substrates to develop epilepsy because dead cells do not seize. The neurons that survive injury sustain permanent long-term plasticity changes in [Ca 2+ ] i and calcium homeostatic mechanisms that are permanent and are a prominent feature of the epileptic phenotype. In the last several years, evidence has accumulated indicating that the prolonged alteration in neuronal calcium dynamics plays an important role in the induction and maintenance of the prolonged neuroplasticity changes underlying the epileptic phenotype. Understanding the role of calcium as a second messenger in the induction and maintenance of epilepsy may provide novel insights into therapeutic advances that will prevent and even cure AE.

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Section: Traumatic Brain Injury-induced Spontaneous Recurrent Seizuresmentioning

confidence: 99%

Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy

DeLorenzo

Sun

Deshpande

2005

Pharmacology & Therapeutics

260

286

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“…One possibility is that CCh causes a dramatic increase in quantal content, although a competing explanation is that CCh promotes synchronous release from somatic and perisomatic GABAergic inputs. Although we did not perform experiments aimed directly at this question, both early speculation and more recent experimental work in area CA1 favors the latter hypothesis (Alger et al 1996;Reich et al 2005).…”

Section: The Role Of Muscarinic Acetylcholine Receptors In Dsimentioning

confidence: 87%

“…These cells are unique among local circuit neurons in the hippocampus and dentate gyrus in that they are glutamatergic rather than GABAergic (Scharfman 1995). They are also extremely sensitive to both ischemia and excitotoxicity (Freund and Magloczky 1993;Hsu and Buzsaki 1993;Magloczky and Freund 1993), have a strong longitudinal projection (Amaral 1978;Amaral and Witter 1989;Buckmaster and Schwartzkroin 1994;Buckmaster et al 1992), and have been consistently implicated (through either their loss or dysfunction) in several competing theories on the etiology of temporal lobe epilepsy (Houser 1999;Lothman et al 1996;Ratzliff et al 2002Ratzliff et al , 2004Santhakumar et al 2000;Sloviter 1991). Our results indicate that excitation of hilar mossy cells produces a robust inhibition of local GABAergic transmission and suggest a prominent role for EC-dependent retrograde signaling in hilar neurophysiology.…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoid-Mediated Depolarization-Induced Suppression of Inhibition in Hilar Mossy Cells of the Rat Dentate Gyrus

Hofmann

Nahir²,

Frazier³

2006

Journal of Neurophysiology

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nabinoid-mediated depolarization-induced suppression of inhibition in hilar mossy cells of the rat dentate gyrus. J Neurophysiol 96: 2501-2512, 2006. First published June 28, 2006 doi:10.1152/jn.00310.2006. Hilar mossy cells represent a unique population of local circuit neurons in the hippocampus and dentate gyrus. Here we use electrophysiological techniques in acute preparations of hippocampal slices to demonstrate that depolarization of a single hilar mossy cell can produce robust inhibition of local GABAergic afferents. This depolarization-induced suppression of inhibition (DSI) can be observed as a transient reduction in frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) or as a transient reduction in amplitude of evoked IPSCs (eIPSCs). We find that DSI of eIPSCs as observed in hilar mossy cells is enhanced by activation of muscarinic acetylcholine receptors, blocked by chelation of postsynaptic calcium, and critically dependent on retrograde activation of presynaptic cannabinoid type 1 (CB1) receptors. We further report that activation of CB1 receptors on GABAergic afferents to hilar mossy cells (by either endogenous or exogenous agonists) preferentially inhibits calcium-dependent exocytosis and that endocannabinoid-dependent retrograde signaling in this system is subject to tight spatial constraints.

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“…An alternative, albeit not mutually exclusive, possibility is that the SGC IML associational collaterals may excite neighboring granule cells, forming a local focus of hyperexcitability after trauma. SGC innervation of surviving mossy cells (Williams et al, 2007) may also contribute to septotemporal spread of excitability (Ratzliff et al, 2004). Given the typical sustained SGC firing, the possibility that SGCs drive early postinjury increases in dentate excitability is compatible with the contribution of polysynaptic network activity to the increase in duration of granule cell and mossy cell firing after brain injury (Santhakumar et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Decrease in Tonic Inhibition Contributes to Increase in Dentate Semilunar Granule Cell Excitability after Brain Injury

Gupta¹,

Elgammal²,

Proddutur³

et al. 2012

J. Neurosci.

106

234

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Brain injury is an etiological factor for temporal lobe epilepsy and can lead to memory and cognitive impairments. A recently characterized excitatory neuronal class in the dentate molecular layer, semilunar granule cell (SGC), has been proposed to regulate dentate network activity patterns and working memory formation. Although SGCs, like granule cells, project to CA3, their typical sustained firing and associational axon collaterals suggest that they are functionally distinct from granule cells. We find that brain injury results in an enhancement of SGC excitability associated with an increase in input resistance 1 week after trauma. In addition to prolonging miniature and spontaneous IPSC interevent intervals, brain injury significantly reduces the amplitude of tonic GABA currents in SGCs. The postinjury decrease in SGC tonic GABA currents is in direct contrast to the increase observed in granule cells after trauma. Although our observation that SGCs express Prox1 indicates a shared lineage with granule cells, data from control rats show that SGC tonic GABA currents are larger and sIPSC interevent intervals shorter than in granule cells, demonstrating inherent differences in inhibition between these cell types. GABA A receptor antagonists selectively augmented SGC input resistance in controls but not in head-injured rats. Moreover, post-traumatic differences in SGC firing were abolished in GABA A receptor blockers. Our data show that cell-type-specific post-traumatic decreases in tonic GABA currents boost SGC excitability after brain injury. Hyperexcitable SGCs could augment dentate throughput to CA3 and contribute substantively to the enhanced risk for epilepsy and memory dysfunction after traumatic brain injury.

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Rapid Deletion of Mossy Cells Does Not Result in a Hyperexcitable Dentate Gyrus: Implications for Epileptogenesis

Cited by 109 publications

References 55 publications

Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy

Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy

Endocannabinoid-Mediated Depolarization-Induced Suppression of Inhibition in Hilar Mossy Cells of the Rat Dentate Gyrus

Decrease in Tonic Inhibition Contributes to Increase in Dentate Semilunar Granule Cell Excitability after Brain Injury

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