Dendritic Hyperpolarization-Activated Currents Modify the Integrative Properties of Hippocampal CA1 Pyramidal Neurons

Abstract

Step hyperpolarizations evoked slowly activating, noninactivating, and slowly deactivating inward currents from membrane patches recorded in the cell-attached patch configuration from the soma and apical dendrites of hippocampal CA1 pyramidal neurons. The density of these hyperpolarization-activated currents (Ih) increased over sixfold from soma to distal dendrites. Activation curves demonstrate that a significant fraction of Ih channels is active near rest and that the range is hyperpolarized relatively more in the distal dendrites. Ih activation and deactivation kinetics are voltage-and temperature-dependent, with time constants of activation and deactivation decreasing with hyperpolarization and depolarization, respectively. Ih demonstrated a mixed Na+-K+ conductance and was sensitive to low concentrations of external CsCl. Dual whole-cell recordings revealed regional differences in input resistance (Rin) and membrane polarization rates (taumem) across the somatodendritic axis that are attributable to the spatial gradient of Ih channels. As a result of these membrane effects the propagation of subthreshold voltage transients is directionally specific. The elevated dendritic Ih density decreases EPSP amplitude and duration and reduces the time window over which temporal summation takes place. The backpropagation of action potentials into the dendritic arborization was impacted only slightly by dendritic Ih, with the most consistent effect being a decrease in dendritic action potential duration and an increase in afterhyperpolarization. Overall, Ih acts to dampen dendritic excitability, but its largest impact is on the subthreshold range of membrane potentials where the integration of inhibitory and excitatory synaptic inputs takes place.

Postnatal maturational properties of rat parafascicular thalamic neurons recorded in vitro

“…For example, we reported previously that there is a developmental increase and then decrease in the percentage of PPN cells expressing Ih over the same period (Kobayashi et al, 2004a). The functional significance of these developmental changes in Ih-expression patterns is an area that deserves further attention, especially in light of the diverse roles of Ih channels in regulating the integrative and firing properties of neurons (Luthi et al, 1998;Magee, 1998;Chen et al, 2002;Robinson and Siegelbaum, 2003). In the PPN, for example, we found that there was a correlation between Ih expression and firing frequency such that those cells with Ih exhibited higher mean depolarization induced firing frequencies compared with non-Ih-expressing cells (Kobayashi et al, 2004a).…”

The role of negative conductances in neuronal subthreshold properties and synaptic integration

“…Reinforcing that negative slope conductance creates amplification of EPSPs, the activation of I h , which is an inward depolarizing current activated by hyperpolarization, decreases the amplitude of EPSPs and reduces their decay time (Magee 1998), similar to the effect of some outward potassium currents (Hoffman et al 1997;Mathews et al 2010). In addition, the inwardly rectifying potassium current, an outward potassium current that has a negative slope conductance region in depolarized potentials, amplifies hyperpolarizations in endothelial cells (Jackson 2016), striatal cholinergic interneurons (Wilson 2005) and vascular smooth muscles (Smith et al 2008), and also amplifies EPSPs in the AP cell of the leech (Wessel et al 1999).…”

PIP2-Mediated HCN3 Channel Gating Is Crucial for Rhythmic Burst Firing in Thalamic Intergeniculate Leaflet Neurons

“…A, Intrinsic temporal summation producing burst firing was initiated by intracellular injection of a train containing five current pulses (100 pA); the protocol shown at bottom was previously described (Ying et al, 2005). EPSC-shaped current pulses were generated with the following function: I(t) ϭ A ϫ (1 Ϫ e Ϫt/ rise ) n e Ϫt/ decay , where A is the infinite time amplitude of the current (in picoamperes), n is an integer, and rise (0.5 ms) and decay (5 ms) are rising and falling time constants, respectively (Magee, 1998) al., Chu et al, 2010;Dembrow et al, 2010). The underlying mechanisms for these effects remain unclear, although Chu et al (2010) suggest that the change is likely due to alteration in other voltagedependent conductances.…”