Previous research suggests that hippocampal neurons in mammalian hibernators shift their major function from memory formation at euthermic brain temperatures (T = ~37 °C) to modulation of hibernation bout duration as T decreases. This role of hippocampal neurons during torpor is based in part on in vivo studies showing that histamine (HA) infused into ground squirrel hippocampi lengthened torpor bouts by ~50%. However, it was unclear if HA acted directly on hippocampal neurons or on downstream brain regions via HA spillover into lateral ventricles. To clarify this, we used hippocampal slices to determine if HA would modulate pyramidal neurons at low levels of synaptic activity (as occurs in torpor). We tested the hypotheses that although LTP (a neuroplasticity mechanism) could not be generated at low temperatures, HA (via H2 receptors) would increase population spike amplitudes (PSAs) of Syrian hamster CA1 pyramidal neurons at low stimulation voltages and low temperatures. PSAs were recorded following Schaffer collateral stimulation from subthreshold levels to a maximum response plateau. We found that tetanus evoked LTP at 35 °C but not 15 °C; and at temperatures from 30 to 15 °C, HA significantly enhanced PSA at near threshold levels in slices from non-hibernating hamsters housed in "summer-like" or "winter-like" conditions and from hibernating hamsters. Cimetidine (H2 antagonist) blocked HA-mediated PSA increases in 8 of 8 slices; pyrilamine (H1 antagonist) had no effect in 7 of 8 slices. These results support our hypotheses and show that HA can directly enhance pyramidal neuron excitability via H2 receptors and thus may prolong torpor bouts.
Previous work showed that histamine (HA) infused into hippocampi excited CA1 pyramidal neurons and lengthened hibernation bouts by 50%. However, HA effectiveness in increasing CA1 pyramidal neuron excitability at low levels of synaptic stimulation (mirroring that when entering torpor) is unknown. We tested the hypotheses that HA modulation of Syrian hamster CA1 pyramidal neurons: increased evoked response amplitude (ERA) to threshold level voltages, persisted at temperatures below 37°C, and involved H2 receptors. We measured CA1 ERAs in response to Schaffer collateral stimulation ranging from near‐maximal saturation (“max”) to below threshold levels at 30°C (n=14) and 20°C (n=17). Addition of 10µM HA to the perfusate increased near‐threshold stimulation ERAs [Taking the max response before HA as 100%, near‐threshold ERAs increased from 2.7% to 12.9% at 30°C (P<0.01), and from 2.5% to 20.7% at 20°C (P<0.001)]. These HA‐mediated increases in ERAs decreased as stimulation intensity approached max. Cimetidine (H2 antagonist; 20 µM) blocked the HA‐mediated ERA increase in 8 of 8 slices stimulated at 50‐75% of saturation. Data support our hypotheses, showing HA enhanced responses near threshold at both 30°C and 20°C, and that HA enhancement was mediated via H2 receptors. Data are consistent with the proposal that HA may modulate a low‐level hippocampal signal to the ascending arousal system to prolong torpor. Grant Funding Source: Supported by UC Davis Provost's Undergraduate Fellowship to KJM
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