Differential frequency-dependent antidromic resonance of the Schaffer collaterals and mossy fibers

To better understand information transfer along the hippocampal pathways and its plasticity, here we studied the antidromic responses of the dentate gyrus (DG) and CA3 to activation of the mossy fibers and Schaffer collaterals, respectively, in hippocampal slices from naïve and epileptic rats. We applied trains of 600 electrical stimuli at functionally meaningful frequencies (θ, β/γ and γ). The responses of the DG to θ frequency trains underwent rapid potentiation that lasted about 400 stimuli, after which they progressively returned to control value. At β/γ and γ frequencies, however, the initial potentiation was followed by a strong frequency-dependent depression within the first 50 stimuli. In kindled animals, the initial potentiation was stronger than in control preparations and the resonant phase at θ frequency lasted longer. In contrast, CA3 responses were exponentially depressed at all frequencies, but depression was significantly less intense at θ frequency in epileptic preparations. Failure of fibers to fire action potentials could account for some of the aforementioned characteristics, but waveforms of the intracellular action potentials also changed as the field responses did, i.e., half-duration and time-to-peak increased in both structures along the stimulation trains. Noteworthy, block of glutamate and GABA ionotropic receptors prevented resonance and reduced the depression of antidromic responses to β/γ and γ stimulation recorded in the DG, but not in CA3. We show that the different behavior in the information transfer along these pathways depends on the frequency at which action potentials are generated, excitability history and anatomical features, including myelination and tortuosity. In addition, the mossy fibers are endowed with ionotropic receptors and terminal active properties conferring them their sui generis non-passive antidromic responses.