Table 2.

Spinule structure and proposed functions in psychiatric disease.

Author, journal, year	Spinule origination and contacts	Cell type and brain region	Human disease or disease model	Microscopy technique, spinule prevalence, and spinule morphology	Proposed spinule functions
Anglade et al., Neurodegeneration, 1996	Postsynaptic spinules originated from spines with perforated PSDs and invaginated afferent terminals of asymmetric synapses	Subcortical caudate nucleus	Parkinson’s disease (PD) versus (vs.) age matched controls	EM; Invaginations resembling spinules more pronounced between two postsynaptic densities	Altered synaptic plasticity and transmission in corticostriatal synapses of PD patients in response to hyperactivity
Sasaki and Iwata, Neurosci Lett, 1999	Not reported; Degenerating presynaptic terminals often displayed spinule-like structures, in one case from the somata	Normal appearing Betz cells in the 5th layer of motor cortex	Amyotrophic lateral sclerosis (ALS) patients vs. age-matched controls	EM; Presynaptic terminals often displayed dark presynaptic vesicles and mitochondria, absent or obscure postsynaptic membranes, and increased spinules in ALS patients	Synaptic alteration in normal-appearing Betz cells in ALS
Zhang and Houser, J Comp Neurol, 1999	Postsynaptic spinules originated from spines with perforated PSDs and protruded into reorganized inner molecular layer presynaptic mossy fiber terminals	Granule cells of the hippocampal dentate gyrus	Temporal lobe epilepsy (TLE) patients	EM; Increased number of spinules extended from perforations in the PSD; Some spinules were elongated and extended into adjacent mossy fiber terminals	Active perforated synapse remodeling and/or multi-synaptic bouton formation to increase granule cell hyperexcitability in TLE; May provide diffusion barrier and increase formation of independent active zones
Popov et al., J Comp Neurol, 2010	Postsynaptic spinules originated from large and complex spines, termed thorny excrescences (TEs)	Hippocampal dentate gyrus and area CA3	Ts65Dn mouse model of Down Syndrome (DS) vs. 2N mice	EM; Decrease in spinule-like protrusions from TEs in Ts65Dn mice	Decreased synaptic plasticity, reduced TE connectivity, synaptic transmission, and down-stream cognitive and memory function in DS
Blanque et al., Front Neuroanat, 2015	Postsynaptic spines	Neocortical and hippocampal neurons	KIBRA knock-out (KO) mice; KIBRA gene has been linked to human memory performance	In KIBRA KO mice, reduced double plasma membrane structures, <0.3 μm in diameter, surrounded by ≥3 synaptic vesicles	Decreased perforated synapses and spinules in KIBRA KO neurons may contribute to impaired long-term synaptic plasticity
Steward et al., Front Mol Neurosci, 2021	Postsynaptic spinules emerged from complex spines with enlarged heads and segmented PSDs and extended into non-degenerating presynaptic terminals	Granule cells of the hippocampal dentate gyrus	C57Bl/6 mice with Wlds mutation, which delays Wallerian degeneration onset vs. wildtype mice, after orphaned axon induction by surgical entorhinal cortex lesion	EM; In Wlds mutant mice, some enlarged spine heads contacting non-degenerating orphaned presynaptic terminals displayed finger-like protrusions	Trans-synaptic signaling processes between orphaned axons and postsynaptic targets to delay axonal degeneration; Multi-synaptic bouton formation