V. Saly et Rd. Andrew, CA3 NEURON EXCITATION AND EPILEPTIFORM DISCHARGE ARE SENSITIVE TO OSMOLALITY, Journal of neurophysiology, 69(6), 1993, pp. 2200-2208
1. The clinical signs of rapidly developing overhydration commonly inc
lude generalized tonic-clonic seizure, which can be combatted by raisi
ng plasma osmolality. How cortical neurons respond to osmotic imbalanc
e has been addressed only recently. In the CA3 cell region of hippocam
pal slices, lowered osmolality (-40 mOsm) rapidly swelled cells, incre
asing field potential amplitude over a period of 8 min and thereby ele
vating field effects and associated neuronal synchronization. 2. Over
a longer time course ( 10-30 min), spontaneous excitatory postsynaptic
potential (EPSP) amplitude gradually increased in 7 of 10 CA3 neurons
recorded intracellularly. In nine additional CA3 cells, hyposmolality
gradually induced combinations of action potential discharge, endogen
ous bursting, and increased synchronized synaptic input. All of these
effects reversed in normosmotic ACSF. 3. Hyperosmotic artificial cereb
rospinal fluid (ACSF) using mannitol reduced field potentials and dram
atically lowered CA3 excitability by reducing spontaneous EPSP amplitu
de and associated bursting. Again, the gradual onset (10-30 min) of ch
anges in spontaneous EPSP amplitude appeared independent of field pote
ntial changes, which were already maximal by 8 min. 4. Cutting mossy f
ibers did not affect the excitability changes induced by osmotic stres
s noted above. The EPSP/inhibitory postsynaptic potential (IPSP) seque
nce evoked from mossy fibers or stratum oriens was unaltered by osmoti
c change and so did not represent osmosensitive afferent input to CA3
neurons. Furthermore, as measured at the soma, resting membrane potent
ial, cell input resistance, and the action potential threshold were un
changed in all cells. It followed that, because the CA3 neurons themse
lves were not responsive, a recurrent excitatory pathway could not rep
resent the osmosensitive input. 5. Because known evoked synaptic pathw
ays were unaffected by osmotic challenge, the actual osmosensitive ele
ments remain unclear. Whatever the mechanism, it is apparent that with
in 30 min, mannitol at clinically relevant concentrations reduces fiel
d effects and excitatory synaptic input to CA3 neurons. Therefore the
anti-epileptiform effects of hyperosmotic agents such as mannitol that
are observed clinically are also apparent in the hippocampal slice at
the level of the single neuron.