CC BY
17
Section CELLULAR NEUROSCIENCE
OM&P
Generation of Multi-Innervated Dendritic Spines in Memory Formation in Ageing
M.G.Stewart1 *, l.Kraev1, W Aziz2 and K.P.Giese2
1 Dept. of Life, Health and Chemical Sciences, The Open University, Milton Keynes, MK7 6AA, UK;
2 Department of Basic and Clinical Neuroscience Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. * Presenting e-mail: m.g.stewart@open.ac.uk
Aims
Aged-related memory decline is associated with impairment of synaptic strengthening, and memory formation in older animals is slower and less flexible in comparison to younger animals. If strengthening is impaired, hippocampus-dependent memory formation depends on modification of neural circuits and in particular the generation of multi-innervated dendritic spines (MIS- Figure 1) (Radwanska et al., 2011, PNAS, 108 (45) 18471-18475). The objectives of this study were to demonstrate the importance of MIS for the persistence of contextual memory in old, but not young, mice.
Fig. 1. MIS - multi-innervated spines Left- Transmission EM with multi-innervated spine (Msp or MIS) contacted by 2 synapses, from axon 1 (axl) and ax2-. Right- 3D reconstruction from serial EM sections of multi-innervated spine (MIS) contacted by 2 presynaptic boutons (PreB,) from 2 axons; PSD, postsynaptic density.
Methods
We have analysed modification of neural circuits and in particular the generation of multi-innervated dendritic spines in the hippocampus before and after contextual fear conditioning (CFC) in wild-type C57BL/6J female mice: young adult (3 months): (i) naïve and (ii) 24 hours after CFC; and in aged mice (18 months): (i) naïve, (ii) 2 hours and (iii) 24 hours after CFC. 3-D reconstructions from serial ultrathin sections were performed for quantitative ultrastructural analyses of structural changes in dendritic spines and post-synaptic densities in hippocampal CA1 stratum radiatum. Two MIS types were analysed: excitatory, with more than one excitatory input from different axons; and dual, which have one excitatory and one inhibitory contact.
Results and conclusions
Mushroom spine number increases significantly after training in young but not aged mice. There is a greater overlap between classes of thin and mushroom spines in young mice after training suggesting a maturation process has occurred, with a transition from thin to mushroom spines. In contrast, aged mice show a separation between frequency classes of thin and mushroom spines where there is an increase in the number of large thin spines not yet transformed into mushroom spines. MIS analyses with excitatory synapse contacts shows that the number of MIS is significantly higher in aged naïve mice compared to young naïve mice. Moreover, training induces a significant increase in MIS number in aged but not young mice. Inhibitory synapse analyses show that both aged and young mice have an increased percentage of inhibitory synapses after training, due to an increase in number of dual MIS (excitatory + inhibitory), but not shaft inhibitory synapses.
Opera Med Physiol 2016 Vol. 2 (S1) 15
