Schaffer collaterals are axon collaterals given off by CA3

pyramidal cell Pyramidal cells, or pyramidal neurons, are a type of multipolar neuron found in areas of the brain including the cerebral cortex, the hippocampus, and the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cor ...

s in the hippocampus. These collaterals project to area CA1 of the hippocampus and are an integral part of memory formation and the emotional network of the Papez circuit, and of the hippocampal trisynaptic loop. It is one of the most studied

synapse In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

s in the world and named after the Hungarian anatomist- neurologist

Károly Schaffer Károly Schaffer (September 7, 1864, Vienna – October 16, 1939, Budapest)In reply to an e-mail query as to the pronunciation of the "a" in "Schaffer" and as to which syllable in "Schaffer" should have the stronger accent, Gabor Gazdag, MD, repli ...

. As a part of the hippocampal structures, Schaffer collaterals develop the

limbic system The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''Ps ...

, which plays a critical role in the aspects of learning and memory. The signals of information from the contralateral CA3 region leave via the Schaffer collateral pathways for the CA1 pyramidal neurons. Mature synapses contain fewer Schaffer collateral branches than those synapses that are not fully developed. Many scientists try to use the Schaffer collateral synapse as a sample synapse, a typical excitatory glutamatergic synapse in the cortex that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well and to develop medication and treatment to cure the chronic diseases, such as dementia and

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

. Moreover, they believe that studying the Schaffer collateral can provide a whole range of understanding how Schaffer collaterals allow us to intervene with drug-treatments and with electrical-stimulation so that the quality of human experience can be improved.

Development

"Schaffer collateral is the

conductor Conductor or conduction may refer to: Music * Conductor (music), a person who leads a musical ensemble, such as an orchestra. * ''Conductor'' (album), an album by indie rock band The Comas * Conduction, a type of structured free improvisation ...

of the orchestra, but not the actual instrument that plays the music" - Dr. Patrick K. Stanto

The functional hippocampus stores long-term memories through synaptic plasticity in terms of storing information. The hippocampus in communication with the

neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...

mediates memory degradation. Plastic changes occurring in the hippocampus are involved in directing the process of memory storage. The Schaffer collateral is involved in activity-dependent plasticity and the information processes that always are processed through the hippocampus all the time. The Schaffer collateral clearly affects whether the target cells fire action potentials or not. However, at the same time, it is triggering the process that takes much longer whereby some

s get stronger and some get weaker, and overall the patterns of

synaptic strength Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

of the network all evolve over time. Moreover, Schaffer collateral axons develop excitatory synapses that are scattered over the

dendritic Dendrite derives from the Greek word "dendron" meaning ( "tree-like"), and may refer to: Biology * Dendrite, a branched projection of a neuron * Dendrite (non-neuronal), branching projections of certain skin cells and immune cells Physical *Dend ...

arborization of hippocampal CA1 pyramidal neurons. In the early stage of long-term potentiation, Schaffer collaterals release

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

that binds to

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synap ...

s of CA1- dendrites. The process of developing a network of CA3-to-CA1 recurrent excitatory glutamatergic synapses alters the frequency of spontaneous action potentials in Schaffer collaterals. By adulthood, CA3 recurrent network activity is reduced, the frequency of spontaneous action potentials is decreased in Schaffer collaterals, and a single release locus synapse with one dendritic spine on a given CA1 pyramidal neuron can be developed by Schaffer collateral axons.

Location

The Schaffer collateral is located between the CA3 region and CA1 region in the hippocampus. Schaffer collaterals are the axons of

s that connect two neurons (CA3 and CA1) and transfer information from CA3 to CA1. The entorhinal cortex sends the main input to the dentate gyrus ( perforant pathway). From the granule cells of the dentate gyrus, connections are made to the CA3 regions of the hippocampus via mossy fibers. CA3 sends the information signals to CA1 pyramidal cells via the Schaffer collateral and commissural fibers from the contralateral hippocampus as well.

Function

Throughout the memory process in the hippocampus, Schaffer collaterals seem not to play a major role in the formation of actual memory, but it is clear that Schaffer collaterals assist the activity-dependent plasticity and the information processes that are always altered over the course of memory development in the hippocampus. Schaffer collaterals alter the development of the

that is critical for

learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machine learning, machines ...

and memory. The contralateral CA3 region sends information through Schaffer collateral to the CA1 pyramidal neurons.

Schaffer collateral and hippocampal synaptic plasticity

Plastic changes occurring in the hippocampus are involved in directing the process by which memories get stored. Schaffer collaterals affect the hippocampus to develop short ( Short-term Plasticity) and long term synaptic plasticity ( Long-term Plasticity) in terms of storing information and changing in the efficiency of synaptic transmission following previous synaptic activity.

Long-term Potentiation

Long-term potentiation (LTP) in the hippocampal formation is an example model for neural plasticity. Schaffer collateral synapses have been used as a sample synapse, a typical excitatory glutamatergic

in the cortex that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well. LTPs are involved in how people store information and how they retrieve information and involve networks of memories that are involved in facts and in emotions as well because the hippocampus is the part of the

connected to the amygdala. LTP in the hippocampus is an important model for neural plasticity that contributes to learning and memory. Schaffer collaterals are the axons of the neurons in the CA3 regions of the hippocampus that form

s in the CA1 regions. The hippocampus is a part of the

feedback Feedback occurs when outputs of a system are routed back as inputs as part of a chain of cause-and-effect that forms a circuit or loop. The system can then be said to ''feed back'' into itself. The notion of cause-and-effect has to be handled ...

process that sends signals to stop

cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...

production. Thus, a damaged hippocampus can cause memory loss and inability of cognitive function. Furthermore, as the hippocampus is the region controlling learning and memory processes, the research on Schaffer collaterals may help to find treatments for diseases related to the hippocampus or its neural processing pathways such as

, a neurodegenerative disorder. Long-term potentiation (LTP) of

at Schaffer collateral

s has largely been attributed to changes in the number and biophysical properties of

s (AMPARs). Neuropsin has a regulatory effect on Schaffer collateral LTP in the rat hippocampus. The functional hippocampus needs to store long-term memories. Once the memories are stored, they remain stored for a long time. Long-term changes in

synaptic efficacy In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuit ...

in the hippocampus can be induced by different patterns of stimulation generating presynaptic and postsynaptic depolarization The theta burst stimulation of Schaffer collaterals can be sufficient to induce LTP by promoting the formation of filamentous actin in CA1 dendrites. Within the mammalian brain, some patterns of synaptic activity produce long-term potentiation (LTP) which is a long-lasting increase in

and long-term depression (LTD) which is a long-lasting decrease in synaptic strength.

LTP at Schaffer collateral-CA1 synapses and "SK2 channel plasticity"

Long-term plasticity in synapses of the hippocampus can be induced by different patterns of stimulation generating pre- and post-synaptic depolarization. These synaptic changes can clearly lead to modification in circuit function and to behavioral plasticity. Some patterns of synaptic activity produce an extensive increase in synaptic strength, also known as Long-Term Potentiation (LTP). In the hippocampus, LTP at Schaffer collateral-CA1 modulates the biophysical properties of AMPA receptors. Moreover, SK2, small-conductance Ca2+-activated

K+ channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of ...

, changes the shape of excitatory postsynaptic potentials (EPSPs) by coupling with N-methyl D-aspartate receptors (

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

s). The research by Lin MT, ''et al.'' was designed to investigate whether SK2 channels participate in synaptic changes when an activity-dependent decrease contributes to LTP. SK2 channels are

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

s that are activated by an increasing in the concentration of intracellular calcium and as a result of allowing K+ cation to cross the cell membrane. The double

immunogold labeling Immunogold labeling or Immunogold staining (IGS) is a staining technique used in electron microscopy. This staining technique is an equivalent of the indirect immunofluorescence technique for visible light. Colloidal gold particles are most ofte ...

identified that SK2 channels and NMDA cohabit within the postsynaptic density (PSD) of CA1 regions of the hippocampus. The authors used theta-burst pairing (TBP) to produce a rapid potentiation of

and to evoke LTP that is induced simultaneously but whose expression levels vary inversely over time, and the result of the TBP induction was compared to the control group. The result showed that the TBP induction of LTP significantly increased EPSPs level. When the stimulus strength was reduced below the action potential threshold, apamin, a

neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...

, was added to assess the contribution of SK2 activity to EPSPs. It resulted in an increase in the level of EPSPs with blockage of SK2 channels. The TBP induction of LTP abolishes SK2 channel contribution to EPSPs. When the induction of chemical LTP was applied, immunoparticles for SK2 were not found within the PSD of asymmetrical synapses. However, the SK2 immunoparticles were observed within intracellular membranes. The activation of protein kinase A (PKA) downregulates the surface expression of SK2 because PKA regulates the surface expression of

s, a non-NMDA-type ionotropic transmembrane receptor, in the hippocampus. Therefore, PKA decreases the activity of LTP-dependent of SK2 channels. See Schaffer collateral#Long-term plasticity.

Short-term plasticity

Short-term synaptic plasticity undergoes important age-dependent changes that have crucial implications during the development of the nervous system.

Vesicular release at "Schaffer Collateral"

Transmitters are released from pre-synaptic terminals through fusion of vesicles to the membrane, that are filled with

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

s such as

. Vesicles are exocytosed, with neurotransmitters reentering the presynaptic terminal for reuse. These fused vesicles then reenter preferentially back into the rapidly recycling pool for reuse. Additional vesicles within the reserve pool of the presynaptic terminal are released according to stronger amplitude

depolarizations In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...

of the presynaptic axon due to greater spatial or temporal summation of action potentials, corresponding to greater calcium influx polarizing. Rate of

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...

is dependent on rate at which vesicles are recycled into the recycling pool. Multivesicular release (MVR) occurs at Schaffer collateral-CA1 synapses when P is elevated by facilitation and that MVR may be a phenomenon common to many synapses throughout the central nervous system.

References

External links

Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. by Collingridge GL. et al.Involvement of Protein Synthesis and Degradation in Long-Term Potentiation of Schaffer Collateral CA1 Synapses by Karpova A. et al.
{{Rostral basal ganglia and associated structures Hippocampus (brain)