Identifying Symmetric and Asymmetric Synapses in the Hippocampus (CA1 Stratum Radiatum)

By Patrick Parker (updated Jan 2017), with notes from Kristen Harris & Josef Spacek.  (Word doc, PDF)

Inhibitory

Location: usually located on the dendritic shaft

Vesicles: “pleiomorphic,” multiple shapes (flattened, oblong, round, etc.), usually smaller than excitatory

PSD width: thin PSD (thinner than nearby spine asymmetric synapse)

Axon: axon synapses with other shafts / inhibitory synapses

A.K.A.: symmetric

Excitatory

Location: usually located on spines, but can be on shafts (esp. aspiny dendrites i.e. interneurons)

Vesicles: typically mostly round vesicles

PSD width: thick PSD (thicker than nearby shaft symmetric synapse)

Axon: axon synapses with other spines / excitatory synapses

A.K.A.: asymmetric

Atlas of Ultrastructural Neurocytology Fig. 1.6.12, http://synapseweb.clm.utexas.edu/16-chemical-synapses-11

Further Tips for Identifying Symmetric and Asymmetric Synapses

(based on discussion with Kristen)

1. Proband: Use a “proband” from that series—find a typical symmetric shaft synapse and a typical asymmetric spine synapse and keep the images handy for comparison. PSD thickness can change based on staining and other local issues, so the comparison must be made to other nearby synapses in that series.

2. PSDs and vesicles: PSDs can vary quite a bit in thickness, even within the symmetric and asymmetric classes. Sometimes an asymmetric PSD might be thin because it is newly-forming or degenerating. Symmetric PSDs might look very thick because they are oblique or en face. And it can be difficult to determine whether vesicles are round or pleiomorphic. All of the criteria must be considered together to make a reasonable decision.

3. Axons: Following the axon is perhaps the strongest method of determining whether a synapse is symmetric or asymmetric. Axons are either excitatory or inhibitory.  So if you are unsure about a synapse but you follow the presynaptic axon to other clearly asymmetric synapses, then the synapse in question is asymmetric.

4. Commonly seen:
            a. Symmetric: commonly seen on the dendritic shaft, base of spine, spine neck, or on a multisynaptic spine head. (Kristen and Josef have never seen nor heard of a symmetric single-synaptic spine head.)

            b. Asymmetric: commonly seen on single-synaptic spine heads, branched spines, or multisynaptic spine heads. They are also seen on dendritic shafts.

            c. Multi: multisynaptic spine heads can be sym/asym or asym/asym, but Kristen and Josef have never seen nor heard of a sym/sym multi.

5. Caveat lector: Note that this protocol is specific to the area studied by the Harris Lab, stratum radiatum of hippocampal CA1. Other brain regions may be significantly different. Josef pointed out a situation we are not used to seeing in hippocampus in Fig. 1.6.10 of the Atlas (http://synapseweb.clm.utexas.edu/16-chemical-synapses-9) – a dendrite containing vesicles makes a reciprocal synapse with an axon, with both sides being pre- and postsynaptic. So these notes should not be taken as rules for the entire brain but rather as guidelines for the specific region we are typically reconstructing.