User:Gordon M. Shepherd/Proposed/Dendro-dendritic synapse

• Dr. Gordon M. Shepherd, Yale University, New Haven, CT

Dendrodendritic synapses directly connect the dendrites of two neurons. Because they enable a cell to send synaptic outputs through its dendrites, they are an exception to the traditional view that neurons receive synaptic inputs in the dendrites (and cell bodies), and send their outputs through their axons. The dendrites have the traditional fine structure of dendrites elsewhere in the nervous system, and the fine structure of the synapses conforms to the traditional type 1 (presumably excitatory) and type 11 (presumably inhibitory). It is believed that these direct synaptic interconnections enable information processing to be carried out in an efficient manner where there is a premium on space and timing. Because they are localized and therefore relatively easily identified, these synaptic patterns are among the best characterized of brain microcircuits.

Locations

Dendrodendritic synapses are found in many regions of the nervous system, of both vertebrates and invertebrates. Table 1 lists some of the best-known sites.

Table 1: Locations of dendrodendritic synapses

Olfactory bulb	Mitral-granule cell interactions	Olfactory glomerulus
Retina	Outer plexiform layer	Inner plexiform layer
Thalamus	Sensory nuclei	Motor nuclei	Reticular nucleus
Neocortex
Globus pallidus
Substantia nigra
Dentate gyrus
Suprachiasmatic nucleus
Red nucleus
Superior colliculus
Raphe nucleus
Locus coerulus
Cerebellum
Pons
Tractus solitarius
Spinal cord	Substantia gelatinosa
Peripheral nervous system	Cochlea
Autonomic nervous system
Invertebrate systems	Stomatogastric ganglion	Locust ganglia	Antennal lobe

Functions

Specific functions of dendrodendritic synapses have been identified or suggested by experimental and computational studies. In the olfactory bulb, side-by-side pairs of synapses mediate mitral-to-granule cell excitation as well as granule-to-mitral cell inhibition. This is believed to provide for feedback inhibition of excited mitral cells, lateral inhibition of less strongly excited mitral cells, and inhibitory gating of mitral cell oscillatory responses. In the retina, dendrodendritic-like reciprocal synapses are found between bipolar cells and amacrine cells, and single dendrodendritic synapses between amacrine cells and ganglion cells. They are believed to be involved in the center-surround organization underlying contrast enhancement. In many thalamic relay nuclei, the main afferents make synapses onto the dendrites of both principal and interneuronal dendrites, the latter of which have dendrodendritic synapses onto the former. This is believed to mediate feedforward inhibition of principal cells to shape their excitatory responses. In the thalamic reticular nucleus dendrodendritic synapses interconnect the dendrites of the reticular cells. A proposed function of this network of inhibitory interneurons is to generate oscillatory activity, particularly for synchronization of thalamic spindles. In the substantia nigra, dopaminergic output cells release dopamine from their dendrites which feedback onto autoreceptors on themselves and neighboring cells. It is speculated that this provides for control of output from these cells, coordinated with release of dopamine onto their axonal targets in the neostriatum.In the spinal cord, the substantia gelatinosa contains complex patterns of axodendritic, dendroaxonic, and dendrodendritic synaptic connections. These form microcircuits that control inputs coming from mechanoreceptors and pain receptors in the skin. In invertebrates, there are many examples of synapses between neurites, which are equivalent to vertebrate dendrites. Examples are found between the neurites of motor neurons in the lobster stomatogastric ganglion, involved in control of motor output, and in the glomeruli of the antennal lobe of insects, involved in initial processing of the olfactory input.

Significance

Beyond their functional roles as indicated above, dendrodendritic synapses have required a revision of traditional concepts of neuronal organization. They show that dendrites can both send synaptic outputs as well as receive them. The local outputs often reflect compartmentalization of the dendritic tree into multiple integrative sites for input-output operations. These operations can be performed without the necessity to generate full-blown action potentials in the axon. The dendritic tree thus comprises multiple layers of integrative operations. Dendrodendritic synapses have subunits and properties similar to those of axo-dendritic synapses, and thus express basic synaptic functional properties of glutamatergic and gabaergic synapses. These include short-term information processing, as well as long-term changes including plasticity, voltage-dependence and long-term modulation, that may be involved in learning and memory.

References

• Shepherd GM. 2004. The Synaptic Organization of the Brain. Fifth Edition. New York: Oxford University Press
• Shepherd GM, Grillner S. 2010. Handbook of Brain Microcircuits. New York: Oxford University Press

Sponsored by: Dr. Gordon M. Shepherd, Yale University, New Haven, CT