Electrical synapses are mechanically and electrically conductive links between two neurons or a neuron and another cell. They occur at gap junctions, the gap being about 3.5 nm wide spanned by proteins called connexins. Six connexins form a connexon unit and two connexon units form a gap junction channel that spans through the presynaptic and postsynaptic membrane.
Since the information is conducted via electric current in gap junctions, the transmission is extremely fast especially in channels that are large in diameter. The speed allows synchronicity of action potentials which seems to be vital for fine timing of motor control.
Electrical synapses, more specifically those formed by connexin 36 (Cx36), are also involved in creating emotional memories. Bissiere et al. blocked either neuronal gap junctions or Cx36 within the dorsal hippocampus on rats testing this hypothesis. The experiment caused significant impairment of context-dependent fear learning, memory, and extinction. (Bissiere et al., 2011) This finding provides understanding of the functional roles of electrical synapses in mechanisms of fear learning and memory in the adult mammalian brain, but it may also point toward new therapeutic treatment of trauma and anxiety disorders.
Most synaptic transmission in the human nervous system is chemical. In chemical synapses, there is a presynaptic and a postsynaptic membrane, separated by a synaptic cleft. The cleft is filled with matrix that “glues” the membranes together. On the presynaptic side of the synapse are vesicles, inside which are the neurotransmitters.The neurotransmitter is the chemical that acts as the means of communication between the presynaptic and postsynaptic neurons. They belong to three categories: amino acids, amines, and peptides. Different neurons release different neurotransmitters and they are synthesized in different ways. On the presynaptic side, protein mass resembling pyramids poke into the cytoplasm of the membrane form the area where neurotransmitters are released, also known as the active zone. The protein mass on the postsynaptic side, called the postsynaptic density, is the area in which the neurotransmitter receptors are. The receptors’ job is to convert the chemical signal from the neurotransmitter into a signal that can be interpreted by other neurons (change in membrane potential or chemical change).
Chemical synaptic transmission contains many steps. The neurotransmitter is synthesized either by proteins already in the neuron or synthesized by specific enzymes. After synthesizing, transporter proteins pack the neurotransmitter into vesicles. The neurotransmitter release is activated by an action potential in the axon terminal. As a consequence, voltage-gated calcium channels in the active zone open up. The increase in calcium concentration causes the neurotransmitter release. The vesicle releases the neurotransmitter into the postsynaptic cleft through exocytosis. This process can be quite fast, sometimes 0.2 msec from the calcium release. After release, the membrane of the vesicle reforms through endocytosis and is recycled to be used again.
In the synaptic cleft neurotransmitters in the synaptic cleft find specific receptor proteins and bind to them. The receptor protein conformation changes and the protein as a result works differently. Neurotransmitter receptors include transmitter gated ion channels and G protein coupled receptors. Transmitter gated ion channels have 4-5 subunits that form a pore, through which ions can pass through when the binding of a neurotransmitter causes the pore to open. If the channel is permeable to Na+, the postsynaptic membrane will depolarize, causing an excitatory postsynaptic potential (EPSP). If it is permeable to Cl-, the membrane will hyperpolarize, causing an inhibitory postsynaptic potential (IPSP). For G protein coupled receptors, neurotransmitters bind to proteins within the postsynaptic membrane, which then cause the activation of G-proteins, which then activate effector proteins. The effects of a neurotransmitter binding to G protein coupled receptors are slower, more long-lasting, and more diverse than voltage gated ion channels.
Synaptic integration is the brain’s form of neuronal computation. A neuron can convert thousands of inputs into an action potential output. This process begins with excitatory postsynaptic potentials (EPSP). Transmitter-gated channels open in the post synaptic membrane bringing an inward depolarizing current, causing the EPSP. The amount of inward current is proportional to the amount of neurotransmitter released from the presynaptic terminal.
Quantal analysis is a method that compares the amplitudes of EPSPs to estimate how many vesicles of neurotransmitters were released by the presynaptic terminal. The quantum is a measure that reflects the number of neurotransmitters in a single vesicle and the number of postsynaptic receptors. EPSPs are integer multiple responses to miniature postsynaptic potentials because of the idea that neurotransmitters are released in packets, or vesicles.
EPSPs are subsequently summed in two ways, spatially and temporally. The EPSPs evoked by different dendrites are summed at the axon hillock. If the potential difference at the axon hillock exceeds a threshold voltage, then an action potential is propagated along the axon. Spatial summation is the summation of multiple EPSPs evoked at different synapses of a dendrite. Temporal summation is the summation of multiple EPSPs evoked in rapid succession at a single synapse (from a single neuron).
EPSPs evoked closer to the axon hillock hold more weight than those that are farther from the axon hillock. This is because the membrane depolarization decays over distance due to inward ionic current “leaking” out of the neuron through ion channels (rm) and loss of potential due to the internal resistance of the neuron (ri). This voltage decay is characterized by a length constant, which is a function of ri and rm. Also, EPSPs that are generated in rapid succession at a synapse hold a lot of weight. Therefore, the location and electrical activity of synapses are very important to the weight the input neuron has on the output neuron’s decision to fire or not.
Similarly, the location and amount of activity of inhibitory synapses holds a lot of weight on the axon hillock potential. Inhibitory synapses usually contain ion channels that allow an influx of anions like chlorine. These kinds of synapses hyperpolarize the membrane potential. They hold a lot more weight the closer they are to the axon hillock. They are analogous to electrical shunts.
Something new we learned in this reading was that the dendrites can have electrically excitable membranes. In other words, they are not always passive. This allows smaller EPSPs to propagate longer distances without dramatic decay. Synaptic integration explains a lot about how certain neurons can hold more weight than others in action potential evocation. It is a critical part to brain wiring and signal propagation.
Bissiere S, Zelikowsky M, Ponnusamy R, Jacobs N, Blair H, Fanselow M. Electrical Synapses Control Hippocampal Contributions to Fear Learning and Memory. Science. Vol 331, Iss. 6013, 2011, pp. 87-91. Available (accessed on 26.9.2020): DOI: 10.1126/science.1193785