Synaptic gating is the ability of neural circuits to gate inputs by either suppressing or facilitating specific synaptic activity. Selective inhibition of certain synapses has been studied thoroughly (see Gate theory of pain), and recent studies have supported the existence of permissively gated synaptic transmission. In general, synaptic gating involves a mechanism of central control over neuronal output. It includes a sort of gatekeeper neuron, which has the ability to influence transmission of information to selected targets independently of the parts of the synapse upon which it exerts its action (see also neuromodulation). Bistable neurons have the ability to oscillate between a hyperpolarized (down state) and a depolarized (up state) resting membrane potential without firing an action potential. These neurons can thus be referred to as up/down neurons. According to one model, this ability is linked to the presence of NMDA and AMPA glutamate receptors. External stimulation of the NMDA receptors is responsible for moving the neuron from the down state to the up state, while the stimulation of AMPA receptors allows the neuron to reach and surpass the threshold potential. Neurons that have this bistable ability have the potential to be gated because outside gatekeeper neurons can modulate the membrane potential of the gated neuron by selectively shifting them from the up state to the down state. Such mechanisms have been observed in the nucleus accumbens, with gatekeepers originating in the cortex, thalamus and basal ganglia.
Gated synapse model
The model for gated synapses was originally derived from the model electronic circuit, in which the gatekeeper serves as a transistor in a circuit. In a circuit, a transistor can act as a switch that turns an electrical signal on or off. In addition, a transistor can serve to amplify an existing current in a circuit. In effect, the gatekeeper neuron acts as the transistor of a gated synapse by modulating the transmission of the signal between the pre-synaptic and post-synaptic neurons. In a model gated synapse, the gate is either open or closed by default. The gatekeeper neuron, therefore, serves as an external switch to the gate at the synapse of two other neurons. One of these neurons provides the input signal and the other provides the output signal. It is the role of the gatekeeper neuron to regulate the transmission of the input to the output. When activated, the gatekeeper neuron alters the polarity of the presynaptic axon to either open or close the gate. If this neuron depolarizes the presynaptic axon, it allows the signal to be transmitted. Thus, the gate is open. Hyperpolarization of the presynaptic axon closes the gate. Just like in a transistor, the gatekeeper neuron turns the system on or off; it affects the output signal of the postsynaptic neuron. Whether it is turned on or off is dependent on the nature of the input signal (either excitatory or inhibitory) from the presynaptic neuron.
Inhibition
Modulation of interneurons Gating can occur by shunting inhibition in which inhibitory interneurons change the membrane conductance of an excitatory target axon, thereby diffusing its excitatory signal. A gating signal from the gatekeeper triggers these inhibitory interneurons in order to prevent one set of neurons from firing even when stimulated by another set. In this state, the gate is closed. Examples of this kind of gating have been found in visual cortical neurons and areas of the prefrontal cortex (PFC) in primates that may be responsible for suppressing irrelevant stimuli. Studies suggest that this kind of inhibition can be attributed in part to GABA receptor-mediated synapses. In order for these inhibitory interneurons to act upon their targets, they must receive input from a gatekeeper signal that stimulates them. This input can be either intrinsic, extrinsic or both. Extrinsic input comes from an area of the brain anatomically and functionally distinct from a given circuit, while intrinsic input is released from parts if the circuit itself. Generally, this input occurs in the form of neuromodulatory substances, such as hormones, neuropeptides and other neurotransmitters that have been released from incoming neurons. These signals then converge on the gatekeeper, where they are integrated and directed toward the target. Depending on the circuit, gate signals may arrive from different brain areas. For example, studies have shown that the entorhinal cortex may gate areas of the medial PFC, thereby inhibiting them from projecting to other brain areas. Additional research has shown that the thalamus can also act as a source for gating signals. In the pathway between the PFC and the hippocampus, stimulation of mediodorsal thalamic neurons, as well as stimulation of ventral tegmental area neurons inhibited PFC neuron firing. These inhibitory effects were shown to be modulated by various dopamine receptor antagonists, which implies some role of dopamine as a neuromodulatory agent in this circuit.
Role in spatial attention Due to the brain's limited capacity to process information, it becomes necessary that the brain have the ability filter out unnecessary information, and select important information. Input, especially to the visual field, competes for selective attention. Models for gating mechanisms in the process of attention have been explored by many groups of researchers, however, a consensus on the role of synaptic gating in attention has not been reached.
Role in working memory
Gating mechanisms in the basal ganglia have been linked to our ability to filter irrelevant information and access relevant information from working memory. In this instance, the gatekeeping function is the responsibility of the thalamus. It opens the gate between two areas in the cortex, allowing for the influence of stimuli in working memory. The thalamus, however, is tonically inhibited by the basal ganglia. Activation within the basal ganglia will allow for the disinhibition of the thalamus and thus, the opening of the gate.
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