Schaffer collaterals are

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action ...

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 co ...

s in the

hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

. These collaterals project to area CA1 of the hippocampus and are an integral part of memory formation and the

emotion Emotions are mental states brought on by neurophysiological changes, variously associated with thoughts, feelings, behavioral responses, and a degree of pleasure or displeasure. There is currently no scientific consensus on a definition. ...

al network of the Papez circuit, and of the

hippocampal The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, an ...

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 fr ...

s in the world and named after the Hungarian

anatomist Anatomy () is the branch of biology concerned with the study of the structure of organisms and their parts. Anatomy is a branch of natural science that deals with the structural organization of living things. It is an old science, having it ...

neurologist Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...

Károly Schaffer. 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. ' ...

, 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 neuron 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. 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 Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/aspartate) system in the body or brain. Examples include excitatory amino acid agonist, excitato ...

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 A chronic condition is a health condition or disease that is persistent or otherwise long-lasting in its effects or a disease that comes with time. The term ''chronic'' is often applied when the course of the disease lasts for more than three mon ...

, such as

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

and Alzheimer's disease. 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 An orchestra (; ) is a large instrumental ensemble typical of classical music, which combines instruments from different families. There are typically four main sections of instruments: * bowed string instruments, such as the violin, viola, c ...

, but not the actual instrument that plays the

music Music is generally defined as the The arts, art of arranging sound to create some combination of Musical form, form, harmony, melody, rhythm or otherwise Musical expression, expressive content. Exact definition of music, definitions of mu ...

" - Dr. Patrick K. Stanto

The functional

stores long-term memories through

synaptic plasticity 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 circui ...

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, ...

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 Activity-dependent plasticity is a form of functional and structural neuroplasticity that arises from the use of cognitive functions and personal experience; hence, it is the biological basis for learning and the formation of new memories. Activit ...

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 potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

s 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 of the network all evolve over time. Moreover, Schaffer collateral

s develop

excitatory synapse An excitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travel, each neuron oft ...

s 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

CA1 pyramidal

neuron A neuron, neurone, or nerve cell is an membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous ...

s. In the early stage of

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 neurons ...

, 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 transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the ce ...

s of CA1-

dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the ...

s. The process of developing a network of CA3-to-CA1 recurrent

excitatory In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...

synapses alters the

frequency Frequency is the number of occurrences of a repeating event per unit of time. It is also occasionally referred to as ''temporal frequency'' for clarity, and is distinct from '' angular frequency''. Frequency is measured in hertz (Hz) which is ...

of spontaneous

s 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 A dendritic spine (or spine) is a small membranous 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 si ...

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

. Schaffer collaterals are the axons of

s that connect two

s (CA3 and CA1) and transfer information from CA3 to CA1. The

entorhinal cortex The entorhinal cortex (EC) is an area of the brain's allocortex, located in the medial temporal lobe, whose functions include being a widespread network hub for memory, navigation, and the perception of time.Integrating time from experience in ...

sends the main input to the

dentate gyrus The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute ...

(

perforant path In the brain, the perforant path or perforant pathway provides a connectional route from the entorhinal cortex to all fields of the hippocampal formation, including the dentate gyrus, all CA fields (including CA1), and the subiculum. Though it ...

way). From the

granule cell A granule is a large particle or grain. It can refer to: * Granule (cell biology), any of several submicroscopic structures, some with explicable origins, others noted only as cell type-specific features of unknown function ** Azurophilic granul ...

s 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 fiber The commissural fibers or transverse fibers are axons that connect the two hemispheres of the brain. In contrast to commissural fibers, association fibers connect regions within the same hemisphere of the brain, and projection fibers connect ...

s from the

contralateral Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...

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

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 and

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered ...

. The

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 The hippocampal formation is a compound structure in the medial temporal lobe of the brain. It forms a c-shaped bulge on the floor of the temporal horn of the lateral ventricle. There is no consensus concerning which brain regions are encompass ...

is an example model for

neural plasticity Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it p ...

. Schaffer collateral synapses have been used as a sample synapse, a typical

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

s as well because the

is the part of the

connected to the

amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex v ...

. LTP in the hippocampus is an important model for

that contributes to learning and memory. Schaffer collaterals are the

s of the

s 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 g ...

production. Thus, a damaged hippocampus can cause

memory loss Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use o ...

and inability of

cognitive function Cognitive skills, also called cognitive functions, cognitive abilities or cognitive capacities, are brain-based skills which are needed in acquisition of knowledge, manipulation of information and reasoning. They have more to do with the mechanisms ...

. Furthermore, as the hippocampus is the region controlling learning and memory processes, the research on Schaffer collaterals may help to find treatments for

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

s related to the hippocampus or its neural processing pathways such as Alzheimer's disease, a

neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

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 neurons ...

(LTP) of synaptic strength 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 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 ...

and

postsynaptic 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 ...

depolarization 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 ess ...

The theta burst stimulation of Schaffer collaterals can be sufficient to induce LTP by promoting the formation of filamentous

actin Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...

in CA1

s. Within the

mammalian brain The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for special sense ...

, some patterns of synaptic activity produce long-term potentiation (LTP) which is a long-lasting increase in synaptic strength and

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 CNS with varying mechanisms dependi ...

(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

can be induced by different patterns of stimulation generating pre- and post-synaptic

. 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 potential In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...

s (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 ...

s that are activated by an increasing in the concentration of intracellular

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

and as a result of allowing K+ cation to cross the cell membrane. The double immunogold labeling identified that SK2 channels and NMDA cohabit within the

postsynaptic density The postsynaptic density (PSD) is a protein dense ''specialization'' attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron. The PSD is in ...

(PSD) of CA1 regions of the

. The authors used theta-burst pairing (TBP) to produce a rapid potentiation of synaptic strength 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

threshold,

apamin Apamin is an 18 amino acid globular peptide neurotoxin found in apitoxin (bee venom). Dry bee venom consists of 2–3% of apamin. Apamin selectively blocks SK channels, a type of Ca2+-activated K+ channel expressed in the central nervous system. ...

, 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 matur ...

, 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 This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...

s. The activation of

protein kinase A In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulatio ...

(PKA) downregulates the surface expression of SK2 because PKA regulates the surface expression of

s, a non-NMDA-type

ionotropic Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...

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 In Biology, biology, the nervous system is the Complex system, highly complex part of an animal that coordinates its Behavior, actions and Sense, sensory information by transmitting action potential, signals to and from different parts of its ...

Vesicular release at "Schaffer Collateral"

Transmitter In electronics and telecommunications, a radio transmitter or just transmitter is an electronic device which produces radio waves with an antenna. The transmitter itself generates a radio frequency alternating current, which is applied to ...

s 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. Neur ...

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

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 The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

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)