Extreme Neuroplasticity of Hippocampal CA1 Pyramidal Neurons in Hibernating Mammalian Species

Abstract

In awake and behaving mammals (with core and brain temperatures at ~37°C), hippocampal neurons have anatomical and physiological properties that support formation of memories. However, studies of hibernating mammalian species suggest that as hippocampal temperature falls to values below ~10°C, CA1 neurons lose their ability to generate long term potentiation (LTP), a basic form of neuroplasticity. That is, the persistent increase in CA3-CA1 synaptic strength following high-frequency stimulation of CA3 fibers (the hallmark of LTP generation at 37°C) is no longer observed at low brain temperatures although the neurons retain their ability to generate action potentials. In this review, we examine the relationship of LTP to recently observed CA1 structural changes in pyramidal neurons during the hibernation cycle, including the reversible formation of hyperphosphorylated tau. While CA1 neurons appear to be stripped of their ability to generate LTP at low temperatures, their ability to still generate action potentials is consistent with the longstanding proposal that they have projections to neural circuits controlling arousal state throughout the hibernation cycle. Recent anatomical studies significantly refine and extend previous studies of cellular plasticity and arousal state and suggest experiments that further delineate the mechanisms underlying the extreme plasticity of these CA1 neurons.

Calcium-Binding Proteins in the Nervous System during Hibernation: Neuroprotective Strategies in Hypometabolic Conditions?

“…At the cell level, these molecular adaptations are paralleled by visible morphological remodeling that has been ascribed to both plastic and neuroprotective strategies. In fact, during hibernation in mammals, a substantial but reversible modification of neural connectivity has been discovered in the hippocampus [146,147] and later in other areas of the encephalon [148], which is characterized by a decrease in cell body area, branching complexity, and spine density, and by an alteration of synaptic protein content [136,149,150]. This retraction is readily reversed during arousal periods, and does not seem to be associated with memory loss [139,151,152,153].…”

Human torpor: translating insights from nature into manned deep space expedition

“…Hibernators have greater resilience against rapid temperature fluctuation‐induced depression in synaptic transmission than non‐hibernating animals (Gabriel, Klussmann & Igelmund, 1998). For mammals, a major function of hippocampal neurons is to support various plasticity mechanisms including long‐term potentiation (LTP), a basic form of neuroplasticity characterized by strengthened and prolonged excitatory postsynaptic potential following high‐frequency stimulation (Horowitz & Horwitz, 2019). In facultative hibernating hamsters, LTP is inducible above 22°C and arrested around 20°C in hippocampal neurons (Krelstein, Thomas & Horowitz, 1990).…”

Neuronal Activity in the Hibernating Brain

“…In vitro approaches (brain slices) have the advantage that cellular mechanisms of neuronal activity in specific types of neurons can be more easily studied. Horowitz and colleagues (Hooper et al, 1985; Eckerman et al, 1990; Horrigan and Horowitz, 1990; Krelstein and Horowitz, 1990; Krelstein et al, 1990; Horowitz and Horwitz, 2019) and Igelmund and colleagues (Igelmund and Heinemann, 1995; Igelmund, 1995; Spangenberger et al, 1995) were pioneers investigating the temperature-dependent properties of CA1 hippocampal pyramidal neurons in brain slices. This early work included the finding that generation of long-term potentiation (LTP) in hamster brain slices is strongly dependent on temperature: i.e., it can be readily elicited above 20°C but not below 15°C (e.g., Krelstein et al, 1990).…”

“…We refer to both earlier and more recent data, thereby focusing on the temperature-dependency of neuronal activity during hibernation. Structural plasticity which underlies functional changes (e.g., synapse and spine degradation, protein synthesis) is not considered here, but was intensively discussed in two recent reviews (Arendt and Bullmann, 2013; Horowitz and Horwitz, 2019).…”