CA3 NEURON EXCITATION AND EPILEPTIFORM DISCHARGE ARE SENSITIVE TO OSMOLALITY

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.