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.

Keywords: LTP; hibernation; hippocampus; memory; neuroplasticity; pyramidal cells (PC).

Figure 1

LTP generation in euthermic animals. (A) CA3-CA1 synaptic structure showing glutamate receptors (AMPARs and an NMDAR) linked to the post-synaptic density (PSD), a multiprotein assembly that orients receptors to face the presynaptic CA3 terminal. Tau is a structural protein that is not highly phosphorylated in the euthermic animal (see text). (B) Electrical circuit for recording CA1 pyramidal neuron-evoked responses. Insert shows evoked response prior to a tetanizing stimulation (basal state) and an enhanced response following the stimulation (LTP-induced). (C) Change in spine head shape before and after tetanizing stimulation. The latter induces a rapid (within seconds) increase in spine head size, allowing insertion of AMPARs into the PSD. Within minutes, the spine head has slightly shrunken to a long lasting (hours) form with additional AMPARs in the PSD (LTP-induced).

Figure 2

CA1 pyramidal cell model for small hibernating mammals (e.g., hamsters, ground squirrels), displaying key reversible adaptations when animal is (A) awake and (B) in torpor. (A) At 37°C, oscillatory hippocampal activity (theta and gamma waves) reflects synchronous excitation of CA1 pyramidal neurons (aligned arrows over afferent fibers). Coincidence gating of NMDARs leads to insertion of more AMPARs in the PSD and synapse strengthening. (B) In torpor, oscillatory activity is attenuated, and intrinsic activity fails to depolarize CA1 pyramidal neurons sufficiently to gate NMDARs. CA1 pyramidal neurons are retracted, spines are reduced in number, and tau is highly phosphorylated. These reconfigured neurons support signal transmission (via AMPARs) from the hippocampus to reticular formation nuclei to prolong hibernation bouts.