| Description |
Hippocampal network oscillations are important for learning and memory. Theta rhythms are involved in attention, navigation, and memory encoding, whereas sharp wave-ripple complexes (ripples) are involved in memory consolidation. Cholinergic neurons in the medial septum-diagonal band of Broca (MS-DB) influence both types of hippocampal oscillations, promoting theta rhythms and suppressing ripples. They also receive frequency-dependent hyperpolarizing feedback from hippocamposeptal connections, potentially affecting their role as neuromodulators in the septohippocampal circuit. However, little is known about how the integration properties of cholinergic MS-DB neurons change with hyperpolarization. By potentially altering firing behavior in cholinergic neurons, hyperpolarizing feedback from the hippocampal neurons may, in turn, change hippocampal network activity. To study how hyperpolarizing inputs change in membrane integration properties, we used whole-cell patch-clamp recordings targeting genetically labeled, choline acetyltransferase-positive neurons in mouse medial septal brain slices. Hyperpolarization of cholinergic MS-DB neurons resulted in a long-lasting decrease in spike firing rate and input-output gain. Additionally, voltage-clamp measures implicated a slowly inactivating, 4-AP-insensitive, outward K+ conductance. Using a conductance-based model of cholinergic MS-DB neurons, we show that the ability of this conductance to modulate firing rate and gain depends on the expression of an experimentally verified shallow intrinsic spike frequency-voltage relationship. Finally, we show that cholinergic suppression of hippocampal ripples can be achieved through an imbalance in drive, caused by cholinergic modulation, to hippocampal excitatory and inhibitory neurons. Together, these findings show possible mechanisms through which cholinergic MS-DB neurons may both influence and be influenced by hippocampal rhythms. |
