The spine apparatus (SA) is a specialized form of

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

(ER) that is found in a subpopulation of

dendritic spines A dendritic spine (or spine) is a small membrane protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical sig ...

in central

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s. It was discovered by

Edward George Gray Edward George Gray (1924–1999) was a British anatomist and neuroscientist who pioneered the investigation of neural tissues with transmission electron microscopy. During his professional career, Gray made a number of profound contributions to ou ...

in 1959 when he applied

electron microscopy An electron microscope is a microscope that uses a beam of electrons as a source of illumination. It uses electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing i ...

to fixed cortical tissue. The SA consists of a series of stacked discs that are connected to each other and to the dendritic system of ER-tubules. The actin binding protein

synaptopodin Synaptopodin is a protein that in humans is encoded by the ''SYNPO'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribe ...

(which was originally described in

podocytes Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule ...

of the kidney) is an essential component of the SA. Mice that lack the gene for synaptopodin do not form a spine apparatus. The SA is believed to play a role in synaptic plasticity, learning and memory, but the exact function of the spine apparatus is still enigmatic.

Morphology

The spine apparatus consists of membranous saccules (discs) and tubules surrounded by wispy filamentous material and is mainly found in large mushroom-shaped

. The wispy filamentous material is the

cytoskeletal The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all Cell (biology), cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane ...

network, mainly

f-actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

, which is responsible for the maintenance and alteration of spine shape. The spine apparatus is connected to the smooth-surfaced

of the

dendrite A dendrite (from Ancient Greek language, Greek δένδρον ''déndron'', "tree") or dendron is a branched cytoplasmic process that extends from a nerve cell that propagates the neurotransmission, electrochemical stimulation received from oth ...

. Consisting of continuous parallel flattened

cisternae A cisterna (: cisternae) is a flattened membrane vesicle found in the endoplasmic reticulum and Golgi apparatus. Cisternae are an integral part of the packaging and modification processes of proteins occurring in the Golgi. Function Proteins begi ...

, the spine apparatus has a large surface area which is important for its function. The spine apparatus occupies a large portion of the volume of the spine stalk, which may increase the longitudinal resistance between spine and dendrite Therefore, the spine apparatus could have a direct effect on the membrane potential of the spine plasma membrane when the synapse is active. The connection to the

smooth endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for "little ne ...

suggests a potential pathway for the transfer of proteins and lipids between the spine and dendrite. The spine apparatus could also function as a reservoir for

calcium ions Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction ...

Function

Local protein synthesis and trafficking

For some time, the function of the spine apparatus has been considered enigmatic. Recent evidence, however, suggests the spine apparatus may possess several distinct functions. After elucidating the structure of the spine apparatus, Spacek and Harris noted a continuation of the smooth endoplasmic reticulum into the spine apparatus, where it then takes on a lamellar structure. This observation suggests the SA might play a role in vesicular transport, although a specific mechanism is not yet clear. Furthermore, Pierce et al. proposed that the spine apparatus may be involved in post-translational protein processing, similar to that observed in the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

, and function in the post-translational processing of GluR1 and GluR2 subunits, which are locally translated in dentritic spines, of

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic glutamate receptor (iGluR) and predominantly sodium ion channel that mediates fast excitator ...

s. The spine apparatus has also been shown to be involved in the post-translational processing and spatial delivery of

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

s, which also function as glutamate receptors and play a significant role in controlling

synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to Chemical synapse#Synaptic strength, strengthen or weaken over time, in response to increases or decreases in their activity. Since memory, memories are postulated to be represent ...

. Considering immunostaining studies have identified NMDARs and AMPARs in the spine apparatus, it has been proposed that the spine apparatus may be critical to the localization of AMPARs and NMDARs to

synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

s during LTP formation. The appearance of

molecular marker In molecular biology and other fields, a molecular marker is a molecule, sampled from some source, that gives information about its source. For example, DNA is a molecular marker that gives information about the organism from which it was taken. ...

s for satellite secretory pathways provides further evidence that the spine apparatus plays a role in local integral membrane protein translocation and processing. More specifically, the protein translocation site marker (Sec61α) and the Golgi cisternae markers (giantin and α-mannosidase II) have been observed in the spine apparatus.

Calcium signaling

Calcium uptake and release by the spine apparatus

Synaptic activity triggers Ca²⁺ influx into

via

s and

voltage-dependent calcium channel Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'' muscle, glial cells, neurons) with a permeability t ...

s. Free Ca²⁺ ions are rapidly removed from the cytoplasm through Na+/Ca2+ exchangers in the plasma membrane and by sarco/endoplasmic reticulum Ca²⁺ ATPases (

SERCA SERCA, or sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, or SR Ca2+-ATPase, is a calcium ATPase-type P-ATPase. Its major function is to transport calcium from the cytosol into the sarcoplasmic reticulum. Function SERCA is a P-type ATPase. It ...

pumps) that mediate Ca²⁺ uptake into the

(sER). The spine apparatus, as a sub-compartment of the sER, has a large surface area and is thought to act as an efficient calcium buffer inside the spine (Figure 2). Recent studies have shown that the spine apparatus is also able to release Ca²⁺ through

inositol trisphosphate receptor Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physi ...

s (IP3Rs) or

ryanodine receptor Ryanodine receptors (RyR) make up a class of high-conductance, intracellular calcium channels present in various forms, such as animal muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissu ...

s (RyRs). The calcium-sensitive nature of IP3Rs and RyRs makes both receptors capable of regenerative

calcium-induced calcium release Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from intracellular Ca2+ stores (e.g., endoplasmic reticulum or sarcoplasmic reticulum). Although CICR was first proposed f ...

(CICR). In dendritic shafts and spines of hippocampal neurons the presence of both RyRs and IP3Rs has been shown by

immunostaining In biochemistry, immunostaining is any use of an antibody-based method to detect a specific protein in a sample. The term "immunostaining" was originally used to refer to the immunohistochemical staining of tissue sections, as first described by ...

. Ca²⁺ release is triggered by glutamate release, activating Group I

metabotropic glutamate receptor The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic receptor, metabotropic process. They are members of the group C GPCR family, group C family of G-protein-coupled r ...

s (mGluRs). The downstream signaling cascade leads to elevated IP₃ levels inside the spine (Figure 2) which trigger Ca²⁺ release events only in those spines that contain sER.Specifically, CICR activates RyR mostly located at the base of dendritic spines, while SERCA pumps are located in the spine head. This asymmetry organization of RyR versus SERCA leads to fast calcium signaling at the base of the dendritic spine, leading to SA calcium depletion. Calcium is finally refilled by ORAI-STIM1 mostly located in clusters in the spine head. The slow calcium influx through this store operated Calcium Entry (SOCE) prevents activation of the RyR triggered by fast synaptic inputs.

Plasticity

The spine apparatus’ ability to release calcium into the cytosol is thought to contribute to the development of

. This was first shown in an experiment using

(SP)-deficient mice, which do not show a spine apparatus in dendritic spines. These SP-deficient mice showed a decrease in

long-term potentiation In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neuron ...

(LTP). Furthermore, LTP1 (short-term plasticity which requires post-translational protein modifications, but is protein synthesis independent), LTP2 (slowly decaying plasticity which is protein synthesis-dependent but does not require gene transcription modifications), and LTP3 (long-lasting LTP that is translation- and transcription-dependent) were decreased as a result of the absence of the spine apparatus. Further studies have shown that altered expression and distribution of RyRs, IP3Rs, and L-type

s (L-VDCCs) can decrease LTP1, LTP2, and LTP3. This observation, combined with the observation that SP-deficient mice have decreased LTP, suggests the proper expression and distribution of calcium channels within the spine apparatus is required for controlling synaptic plasticity. Moreover, the spine apparatus is critical for maintaining the cytosolic calcium levels which are central to the formation of synaptic plasticity. SP-deficient mice also exhibited behavioral changes, including decreased horizontal

locomotor activity Locomotor activity is a measure of animal behavior which is employed in scientific research. Hyperlocomotion, also known as locomotor hyperactivity, hyperactivity, or increased locomotor activity, is an effect of certain drugs in animals in whi ...

, decreased anxiety, and a decreased ability to acquire LTP3-related spatial memory, as shown in a

radial arm maze The radial arm maze was designed by Olton and Samuelson in 1976 to measure spatial learning and memory in rats. The original apparatus consists of eight equidistantly spaced arms, each about 4 feet long, and all radiating from a small circular cen ...

. The decreased locomotor activity and decreased spatial learning suggest the spine apparatus’ role in inducing cerebellar LTP, in addition to hippocampal LTP. The exact mechanisms of these deficiencies are not fully understood. These behavioral modifications are thought to be epiphenomena of the absence of a spine apparatus and the changes in cytosolic calcium control mechanisms typically provided by the spine apparatus.

Synaptopodin Synaptopodin is a protein that in humans is encoded by the ''SYNPO'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribe ...

, a protein that binds

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

and α-actinin-2, is closely associated with the spine apparatus. Although SP-deficient mature mice both lack the spine apparatus and display impaired LTP, the relationship between SP, the spine apparatus, and plasticity is complicated by the following three findings: (1) In addition to being associated with the spine apparatus, SP is also located in the cisternal organelle, which is structurally similar to the spine apparatus. (2) The spine apparatus is generally found in mushroom spines of mature neurons, but ample levels of SP and expression of LTP have been detected in juvenile rats just 15 days old. (3) Unlike SP, the spine apparatus has not been found in cultured neurons. These findings have led some to the conclusion that the spine apparatus is implicated in plasticity only because this organelle is associated with SP. Direct evidence for an essential function of the spine apparatus in mGluR-dependent

long-term depression In neurophysiology, long-term depression (LTD) is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus. LTD occurs in many areas of the Central Nervous System, CNS with v ...

(LTD) has been provided by comparing plasticity of synapses on spines with or without spine apparatus. In this study, only synapses associated with sER displayed this form of depression. Blocking IP3-mediated Ca²⁺ release blocked synaptic depression, indicating a causal role of the spine apparatus in the induction of mGluR-dependent LTD.

References

{{reflist

External links

Synapse Web: Electron microscopy of the spine apparatus
Organelles