Multiple Forms of Long-Term Potentiation and Long-Term Depression Converge on a Single Interneuron in the Leech CNS

Abstract

Long-term potentiation (LTP) of synaptic transmission was observed in two types of synapses that converge on the same postsynaptic neuron in the leech CNS. These synapses were made by identifiable sensory neurons, the mechanosensory touch (T-) and pressure (P-) cells, onto the S-cell, an interneuron critical for certain forms of learning. Changes in both the T-S and P-S synapses appear to be activity dependent because LTP was restricted to inputs that had undergone tetanization; however, properties of synaptic plasticity at the T-S and P-S connections differ considerably. At the P-S synapse, LTP was induced in the tetanized synapse but not in the nontetanized synapse tested in parallel. P-S LTP was blocked by the NMDA receptor antagonist DL-2-amino-5-phosphono-valeric acid (AP-5) or by lowering the extracellular concentration of glycine, an NMDA receptor (NMDAR) co-agonist. P-S LTP was strongly affected by the initial amplitude of the synaptic potential at the time LTP was induced. Smaller amplitude synapses (Ͻ3.5 mV) underwent robust potentiation, whereas the less common, larger amplitude synapse (Ͼ3.5 mV) depressed after tetanization. At the T-S synapse, tetanization simultaneously induced homosynaptic LTP in the tetanized input and heterosynaptic long-term depression (LTD) in the input made by a nontetanized T-cell onto the same S-cell. Interestingly, AP-5 failed to block homosynaptic LTP at the T-S synapse but did prevent heterosynaptic LTD. T-S LTP was not affected by the initial EPSP amplitude. Thus, leech neurons exhibit synaptic plasticity with properties similar to LTP and LTD found in the vertebrate nervous system.

Co-induction of long-term potentiation and long-term depression at a central synapse in the leech

“…This pattern of homLTP and hetLTD (synapses consisting of different presynaptic cells, but the same postsynaptic target) has been observed in the CA1 (Lynch et al, 1977), CA3 (Kosub et al, 2005) and dentate gyrus (Abraham and Goddard, 1983) regions of the hippocampus, the amygdala (Royer and Pare, 2003) and the visual cortex (Tsumoto and Suda, 1979). HomLTP at the T→S synapse is NMDAR-independent while T→S hetLTD is NMDAR-dependent (Burrell and Sahley, 2004). In this study, we examined underlying homLTP at the T→S synapse and discovered that inhibition of homLTP uncovered LTD in the same synapse that was apparently initiated in parallel with LTP in the tetanized pathway.…”

“…However, it is now apparent that NMDAR-dependent signaling processes are not the only form of LTP operating in the brain (Malenka and Bear, 2004). Previously, we have observed that LTP in leech central synapses made by the touch mechanosensory neurons onto the S interneuron was NMDAR-independent (Burrell and Sahley, 2004). Here we examine the cellular mechanisms mediating T-to-S (T→S) LTP and find that its induction requires activation of metabotropic glutamate receptors (mGluRs), voltage-dependent Ca 2+ channels (VDCCs) and protein kinase C (PKC).…”

“…1A), which is the focus of this paper, tetanic stimulation simultaneously induces homosynaptic LTP (homLTP) in the tetanized synapse and heterosynaptic LTD (hetLTD) in the non-tetanized synapse ( Fig. 1B; also see Burrell and Sahley, 2004). This pattern of homLTP and hetLTD (synapses consisting of different presynaptic cells, but the same postsynaptic target) has been observed in the CA1 (Lynch et al, 1977), CA3 (Kosub et al, 2005) and dentate gyrus (Abraham and Goddard, 1983) regions of the hippocampus, the amygdala (Royer and Pare, 2003) and the visual cortex (Tsumoto and Suda, 1979).…”

“…The S-cell is thought to be critical for certain types of learning in the leech (Modney et al, 1997;Burrell et al, 2003). LTP in the P→S synapse is NMDARdependent, synapse-specific, and expressed postsynaptically (Burrell and Sahley, 2004). At the T→S synapse (Fig.…”

“…Intracellular recordings from identified T-and S-cells were made using glass sharp microelectrodes connected to a bridge amplifier (BA-1; National Precision Instruments). A detailed protocol for inducing homLTP and hetLTD in the T→S synapse are described in Burrell and Sahley (2004). In brief, unitary excitatory postsynaptic potentials (EPSPs) were elicited in the S-cell by stimulation of the presynaptic neuron (the T-cell) prior to (pre-test) and 1 hr after (post-test) tetanic stimulation of the dorsal posterior nerve root.…”