Downregulation of DendriticI_hin CA1 Pyramidal Neurons after LTP

Abstract

Hyperpolarization-activated (h)-channels occupy a central position in dendritic function. Although it has been demonstrated that these channels are upregulated after large depolarizations to reduce dendritic excitation, it is not clear whether they also support other forms of long-term plasticity. We show here that nearly maximal long-term potentiation (LTP) induced by theta-burst pairing produced upregulation in h-channel activity in CA1 pyramidal neurons. In contrast, moderate LTP induced by spike-timing-dependent plasticity or high-frequency stimulation (HFS) downregulated the h-current (Ih) in the dendrites. After HFS-induced LTP, the h-conductance (Gh) was reduced without changing its activation. Pharmacological blockade ofIhhad no effect on LTP induction, but occluded EPSP-to-spike potentiation, an input-specific facilitation of dendritic integration. Dynamic-clamp reduction ofGhlocally in the dendrite mimicked the effects of HFS and enhanced synaptic integration in an input-selective way. We conclude that dendriticIhis locally downregulated after induction of nonmaximal LTP, thus facilitating integration of the potentiated input.

Axon Physiology

“…Originally described in the dentate gyrus of the hippocampus, E-S potentiation was also found at the Schaffer collateral-CA1 cell synapse when the afferent fibers were tetanized (1,9,136) and maybe induced associatively with coincident activation of synaptic input and a back-propagated action potential (91). Although dendritic conductances such as A-type K ϩ (199) or h-type currents (90) are implicated in its expression, regulation of axonal channels cannot totally be excluded. Indeed, hyperpolarization of the spike threshold has been encountered in many forms of long-lasting increase in excitability in cerebellar and hippocampal neurons (3,568).…”

Tonic Nanomolar Dopamine Enables an Activity-Dependent Phase Recovery Mechanism That Persistently Alters the Maximal Conductance of the Hyperpolarization-Activated Current in a Rhythmically Active Neuron

“…Chronic changes in activity, seizures and sensory deprivation can persistently alter I h expression (Brewster et al, 2002;Gibson et al, 2006;Arimitsu et al, 2009;Hassfurth et al, 2009). Changes in I h accompany LTP and LTD (van Welie et al, 2004;Fan et al, 2005;Brager and Johnston, 2007;Campanac et al, 2008), and it has been suggested that I h is an effector for activity-dependent homeostatic plasticity . Resonance frequency is variable in CA1 pyramidal neurons such that the increase in I h that accompanied LTP increased resonance frequency, suggesting that neurons may tune their resonance frequencies to the inputs they receive (Narayanan and Johnston, 2007).…”

Visual-Induced Excitation Leads to Firing Pauses in Striatal Cholinergic Interneurons

“…Finally, in behaving animals, thalamic neurons respond strongly to sensory stimuli during conditions when neither TANs nor DA neurons respond (Matsumoto et al, 2001), making it likely that the DA projection contributes independently from thalamic inputs to enable TAN responses. Possible indirect roles for the DA input might include induction of short-term (Salgado et al, 2005) or longterm synaptic plasticity that boosts the impact of depolarizing synaptic inputs to CINs, or DAdependent modulation of dendritic integration in CINs through downregulation of I H (Nolan et al, 2004;Campanac et al, 2008). Although it is clear that DA plays some role in the expression of pause responses of TANs, the exact mechanisms need to be elucidated through further research.…”