Theta rhythm of hippocampal CA1 neuron activity: gating by GABAergic synaptic depolarization

Information processing and memory consolidation during exploratory behavior require synchronized activity known as hippocampal theta (theta) rhythm. While it is well established that the theta activity depends on cholinergic inputs from the medial septum/vertical limb of the diagonal band nucleus (MS/DBv) and theta discharges of GABAergic interneurons, and can be induced with cholinergic receptor agonists, it is not clear how the increased excitation of pyramidal cells could occur with increased discharges of GABAergic interneurons during theta waves. Here, we show that the characteristic theta activity in adult rat hippocampal CA1 pyramidal cells is associated with GABAergic postsynaptic depolarization and a shift of the reversal potential from Cl(-) toward HCO(3)(-) (whose ionic gradient is regulated by carbonic anhydrase). The theta activity was abolished by GABA(A) receptor antagonists and carbonic anhydrase inhibitors, but largely unaffected by blocking glutamate receptors. Carbonic anhydrase inhibition also impaired spatial learning in a water maze without affecting other sensory/locomotor behaviors. Thus HCO(3)(-)-mediated signaling, as regulated by carbonic anhydrase, through reversed polarity of GABAergic postsynaptic responses is implicated in both theta and memory consolidation in rat spatial maze learning. We suggest that this mechanism may be important for the phase forward shift of the place cell discharges for each theta cycle during the animal's traversal of the place field for that cell.