Positive Feedback from Hilar Mossy Cells to Granule Cells in the Dentate
Gyrus Revealed by Voltage-Sensitive Dye and Microelectrode Recording.
Jackson, Meyer B. and Helen E. Scharfman.
Department of Physiology and Center for Neuroscience, University of
Wisconsin, Madison, WI 53706, Neurology Research Center, Helen Hayes Hospital,
NY State Department of Health, W. Haverstraw NY 10993 and Departments of
Pharmacology and Neurology, Columbia College of Physicians and Surgeons, New
York, NY 10032.
APStracts 3:0020N, 1996.
SUMMARY AND CONCLUSIONS
1. Microelectrode recording and fluorescence measurement with voltage-
sensitive dyes were employed in horizontal hippocampal slices from rat to
investigate responses in the dentate gyrus to molecular layer and hilar
stimulation. 2. Both field potential and dye fluorescence measurement revealed
that electrical stimulation of the molecular layer produced strong excitation
throughout large regions of the dentate gyrus at considerable distances from
the site of stimulation. 3. Treatment of slices with the excitatory amino acid
receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-
amino-5-phosphonovaleric acid (APV) unmasked dye fluorescence signals in the
outer and middle molecular layers corresponding to action potentials in axons,
presumably belonging to the perforant path. The spread of these axonal signals
away from the site of stimulation was far less extensive than the spread of
control signals through the same regions prior to blockade of excitatory
synapses. Large control responses could be seen in regions distant from the
stimulation site where the axonal signals were not detectable. A lack of
correlation between control signals and axonal signals revealed by DNQX and
APV supports the hypothesis that responses in distal regions of the molecular
layer were not dependent on perforant path axons. 4. The perforant path was
cut by producing a lesion in the outer two thirds of the molecular layer. Both
dye fluorescence and microelectrode recording showed that stimulation on one
side of the lesion could produce signals on the same side as well as across
the lesion. The lesion did not block the spread of excitation through the
molecular layer. Across the lesion from the site of stimulation, negative-
going field potentials were observed to peak in the inner molecular layer,
which is the major field of projection of hilar mossy cells. 5. Electrical
stimulation in the hilus adjacent to the granule cell layer evoked dye
fluorescence responses in the molecular layer. Stimulation at this site evoked
negative-going field potentials that peaked in the inner molecular layer.
These signals were sensitive to excitatory amino acid receptor antagonists but
not to GABA a receptor antagonists. 6. Activation of excitatory amino acid
receptors in the hilus by focal application of (+/-)- [alpha] -amino-3-
hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid
(NMDA) elicited negative-going field potentials in the granule cell layer and
depolarization of granule cells. Field potentials were blocked by tetrodotoxin
(TTX) indicating that they were not caused by direct activation of receptors
on granule cells, but rather by synapses from hilar neurons on granule cells.
7. These results taken together with previous studies of hilar mossy cells
suggest a fundamental circuit consisting of granule cells exciting hilar mossy
cells, which then excite more granule cells. This circuit provides positive
feedback and can be considered a form of "recurrent excitation" unique to the
dentate gyrus. The robustness of this circuit in hippocampal slices under
control conditions suggest that mossy cell excitation of granule cells could
play an important role in the normal activity of the hippocampus, and when
inhibition is compromised this circuit could contribute to the generation and
spread of seizures.
Received 17 August 1995; accepted in final form 5 January 1995.
APS Manuscript Number J541-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96