9 ± 11.1 pA, KO = 264.0 ± 29.4 pA, p = 0.070) or the number of spikes evoked in response to a series of increasing steps of current injection (p = 0.328, F = 0.992) (see Figure S1 available online; CT n = 14; KO n = 15). Additionally, the input-output curve revealed no significant difference in conductance, except at the most negative (−320 pA) current step, an effect consistent with the smaller sag seen in the KO group (Figure S1). Analysis of action potential burst firing, a characteristic feature of CA3 neurons, yielded no significant difference between KO and CT groups selleck compound in either inter-spike interval (mean: CT = 33.0 ± 1.4 ms, n = 14; KO = 32.0 ± 1.3 ms,
n = 13, p = 0.815) or percent spikes fired in a burst (CT = 16.9% ± 3.1%, n = 14; KO = 13.5% ± 4.2%, n = 13, p = 0.517; Figure S2). Furthermore,
93% of control CA3 pyramidal cells displayed burst activity at GSK-3 activation the 600 pA step, whereas 77% of recorded neurons in knockout mice showed bursting behavior, suggesting that CA3 neurons in the KO mice are not inherently more excitable or likely to burst than cells in littermate controls. To determine whether HCN1 deletion altered spatial encoding in the hippocampus, place cell properties were measured as mice were allowed to run for 10–15 min in one of two enclosures, (1) a square box (50 × 50 cm) or (2) a 100 cm long track (referred to hereafter as box or track). We did not observe any differences in running/stopping behaviors in the two groups of mice. Place cell recordings were obtained in the dorsal hippocampus from proximal regions of CA1 and CA3 (1.8 ± 0.06 mm lateral from midline); there was no difference in cell sampling in knockout and control mice (Figure S4). We compared CA1 and CA3 place field size, stability, coherence and information
content in HCN1 knockout mice and their much control littermates. Place field size was measured as percentage of total area in which a neuron fired above background in either the box or track enclosures (see Experimental Procedures). The fields were somewhat larger in the track (Figures 1B and 2B) than in the box (Figures 1A and 2A). For place cells in both CA1 (Figure 1) and CA3 (Figure 2) regions, the size of the place fields in knockout mice was significantly larger than in control mice. In the box, CA1 place fields (Figure 3A, left) were on average 55.3% larger (p = 0.004, t = 2.97, df = 83) in knockout mice (percent area = 32.3% ± 2.75%) compared to control mice (percent area = 20.8% ± 1.55%). In the track (Figure 3A, right), deletion of HCN1 resulted in a similar increase in CA1 place field size; there was a 52.8% increase in place fields (p = 0.002, t = 3.21, df = 70) in the knockout mice (percent area = 37.9% ± 2.55%) compared to littermate controls (percent area = 24.8% ± 1.8%). Although CA3 place field size was also increased upon HCN1 deletion, the effect was significantly less than that seen in CA1. In the box (Figure 3B, left) CA3 place fields were 25.5% larger (p = 0.