Faculty Opinions recommendation of Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus.

Lieberman, David N. and Istvan Mody. Substance P enhances NMDA channel function in hippocampal dentate gyrus granule cells. J. Neurophysiol. 80: 113–119, 1998. Substance P (SP)–containing afferents and the NK-1 tachykinin receptor to which SP binds are present in the dentate gyrus of the rat; however, direct actions of SP on principal cells have not been demonstrated in this brain region. We have examined the effect of SP on N-methyl-d-aspartate (NMDA) channels from acutely isolated dentate gyrus granule cells of adult rat hippocampus to assess the ability of SP to regulate glutamatergic input. SP produces a robust enhancement of single NMDA channel function that is mimicked by the NK-1–selective agonist Sar9, Met(O2)11-SP. The SP-induced prolongation of NMDA channel openings is prevented by the selective NK-1 receptor antagonist (+)-(2 S,3 S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994). Calcium influx or activation of protein kinase C were not required for the SP-induced increase in NMDA channel open durations. The dramatic enhancement of excitatory amino acid–mediated excitability by SP places this neuropeptide in a key position to gate activation of hippocampal network activity.

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Regionally Localized Recurrent Excitation in the Dentate Gyrus of a Cortical Contusion Model of Posttraumatic Epilepsy

Journal of Neurophysiology ◽

10.1152/jn.00957.2009 ◽

2010 ◽

Vol 103 (3) ◽

pp. 1490-1500 ◽

Cited By ~ 46

Author(s):

Robert F. Hunt ◽

Stephen W. Scheff ◽

Bret N. Smith

Keyword(s):

Head Injury ◽

Dentate Gyrus ◽

Action Potentials ◽

Granule Cells ◽

Mossy Fiber ◽

Granule Cell Layer ◽

Mossy Fiber Sprouting ◽

Posttraumatic Epilepsy ◽

Dentate Granule Cells ◽

Cortical Contusion

Posttraumatic epilepsy is a frequent consequence of brain trauma, but relatively little is known about how neuronal circuits are chronically altered after closed head injury. We examined whether local recurrent excitatory synaptic connections form between dentate granule cells in mice 8–12 wk after cortical contusion injury. Mice were monitored for behavioral seizures shortly after brain injury and ≤10 wk postinjury. Injury-induced seizures were observed in 15% of mice, and spontaneous seizures were observed weeks later in 40% of mice. Timm's staining revealed mossy fiber sprouting into the inner molecular layer of the dorsal dentate gyrus ipsilateral to the injury in 95% of mice but not contralateral to the injury or in uninjured controls. Whole cell patch-clamp recordings were made from granule cells in isolated hippocampal brain slices. Cells in slices with posttraumatic mossy fiber sprouting had an increased excitatory postsynaptic current (EPSC) frequency compared with cells in slices without sprouting from injured and control animals ( P < 0.001). When perfused with Mg2+-free artificial cerebrospinal fluid containing 100 μM picrotoxin, these cells had spontaneous bursts of EPSCs and action potentials. Focal glutamate photostimulation of the granule cell layer evoked a burst of EPSCs and action potentials indicative of recurrent excitatory connections in granule cells of slices with mossy fiber sprouting. In granule cells of slices without sprouting from injured animals and controls, spontaneous or photostimulation-evoked epileptiform activity was never observed. These results suggest that a new regionally localized excitatory network forms between dentate granule cells near the injury site within weeks after cortical contusion head injury.

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