The gray area between synapse structure and function—Gray's synapse types I and II revisited

Abstract

On the basis of ultrastructural parameters, the concept was formulated that asymmetric Type I and symmetric Type II synapses are excitatory and inhibitory, respectively. This "functional Gray synapses concept" received strong support from the demonstration of the excitatory neurotransmitter glutamate in Type I synapses and of the inhibitory neurotransmitter γ-aminobutyric acid in Type II synapses, and is still frequently used in modern literature. However, morphological and functional evidence has accumulated that the concept is less tenable. Typical features of synapses like shape and size of presynaptic vesicles and synaptic cleft and presence of a postsynaptic density (PsD) do not always fit the postulated (excitatory/inhibitory) function of Gray's synapses. Furthermore, synapse function depends on postsynaptic receptors and associated signal transduction mechanisms rather than on presynaptic morphology and neurotransmitter type. Moreover, the notion that many synapses are difficult to classify as either asymmetric or symmetric has cast doubt on the assumption that the presence of a PsD is a sign of excitatory synaptic transmission. In view of the morphological similarities of the PsD in asymmetric synapses with membrane junctional structures such as the zonula adherens and the desmosome, asymmetric synapses may play a role as links between the postsynaptic and presynaptic membrane, thus ensuring long-term maintenance of interneuronal communication. Symmetric synapses, on the other hand, might be sites of transient communication as takes place during development, learning, memory formation, and pathogenesis of brain disorders. Confirmation of this idea might help to return the functional Gray synapse concept its central place in neuroscience.

Mapping and morphometric analysis of synapses and spines on fusiform cells in the dorsal cochlear nucleus

“…In addition, when multiple active zones were found in a given synaptic terminal, some active zones were flanked on the postsynaptic side by distinct PSDs while others were not. An alternative interpretation of our results is that the presence or absence of PSD may reflect different degrees of synaptic stability, as recently discussed by Klemann and Roubos (2011). Accordingly, synapses with well-developed PSDs represent more established and more stable connections, while those without PSDs or with poorly developed PSDs are more transitional.…”

“…Based on the presence or absence of PSDs, we differentiated synapses into the same two categories used by others, including asymmetric (Gray Type I synapses) which possess PSDs and symmetric (Gray Type II) which lack PSDs (see review of Klemann and Roubos, 2011). We quantified the relative numbers of these two types of synapses in each synaptic compartments of the cell.…”

“…Many studies have adopted the concept that that asymmetric synapses are excitatory while symmetric synapses are inhibitory (see review of Klemann and Roubos, 2011). Based on this premise and the fact that most of the synapses we observed on dendritic spines of fusiform cells were asymmetric while those on the soma were predominantly symmetric, our results are not inconsistent with the view that axo-spinous synapses on fusiform cells are mostly excitatory while axo-somatic synapses are mostly inhibitory.…”

Gonadotropin-Releasing Hormone Neurones Innervate Kisspeptin Neurones in the Female Mouse Brain

“…Although exceptions have been reported, this asymmetric morphology usually reflects excitatory neurotransmission [65]. The presence of the glutamatergic marker, VGLUT2, in most GnRH neurones in rats and mice [66,67] is consistent with putative excitatory glutamatergic transmission from GnRH neurones at the synapses in question.…”

A method for the three-dimensional reconstruction of Neurobiotin™-filled neurons and the location of their synaptic inputs

“…Pioneering work has linked pre-synaptic structures (vesicular formation and active zone) and post-synaptic densities at the ultra-structural level to defined sites on the neuron soma-dendritic axis (Gray, 1959; Uchizono, 1965; Colonnier, 1968), see (Klemann and Roubos, 2011) for a recent review on this topic). The terms asymmetric synapses (also known as Type I and nominally excitatory) and symmetric synapses (Type II and nominally inhibitory) derive from the same studies.…”