Progressive recovery of learning during regeneration of a single synapse in the medicinal leech

Burrell, Brian D.; Sahley, Christie L.; Muller, Kenneth J.

doi:10.1002/cne.10530

Cited by 30 publications

(40 citation statements)

References 44 publications

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“…Serotonin depletion is know to disrupt, but not eliminate, associative learning of leech shortening (Sahley, 1994), suggesting that other types of neuroplasticity, including LTP and LTD, may contribute to this form of learning. Although it is not known whether the S-cell plays a role in associative learning of reflexive shortening, it is an attractive candidate given its critical role for sensitization and full dishabituation of reflexive shortening (Sahley et al, 1994b;Modney et al, 1997;Burrell et al, , 2003. In addition, because the S-interneuron network extends throughout the leech CNS (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The S-cell was chosen because of its role in learning-related behavioral plasticity of the whole-body shortening reflex: the interneuron is critical for the induction and maintenance of sensitization of shortening and also contributes to dishabituation of this reflex (Sahley et al, 1994b;Modney et al, 1997;Burrell et al, , 2003. Given its importance for sensiti-zation, the S-cell also may be a site for activity-dependent forms of neuroplasticity thought to contribute to associative types of learning.…”

Section: Introductionmentioning

confidence: 99%

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

Burrell¹,

Sahley²

2004

J. Neurosci.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Burrell¹,

Sahley²

2004

J. Neurosci.

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“…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).…”

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confidence: 99%

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

Burrell

2008

Neurobiology of Learning and Memory

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Most studies of long-term potentiation (LTP) have focused on potentiation induced by the activation of postsynaptic NMDA receptors (NMDARs). 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). Surprisingly, whenever LTP was pharmacologically inhibited, long-term depression (LTD) was observed at the tetanized synapse, indicating that LTP and LTD were activated at the same time in the same synaptic pathway. This co-induction of LTP and LTD likely plays an important role in activity-dependent regulation of synaptic transmission. Keywordsmetabotropic glutamate receptor; voltage-dependent Ca 2+ channel; protein kinase C; neuroplasticity; invertebrate NMDAR-dependent long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical cellular substrates for mediating learning and memory because their initiation requires coincident activity in both the pre-and postsynaptic neurons (activity dependence) and the resulting changes are restricted to the co-activated synapses (synapse specificity). However, it is now clear that other molecules can perform coincidence-detection in place of NMDARs for both LTP and LTD (Malenka and Bear, 2004;Anwyl, 2006). This heterogeneity in cellular mechanisms mediating LTP and LTD, along with the structural complexity of the vertebrate brain, complicates efforts to determine the functional contribution of synaptic changes to learning-related changes in behavior. The medicinal leech (Hirudo medicinalis) has a number of properties that make it a useful model for studies of LTP and LTD. Most neurons in the leech CNS are large and easily visualized and there are far fewer neurons in the leech CNS (~400 neurons/ganglion with 21 body ganglia plus the head and tail ganglia )) compared to a mammalian brain. Therefore, it is possible to record

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“…Such changes are usually at the level of individual synapses, both pre-and postsynaptic (Nicoll and Malenka, 1995;Roberts and Glanzman, 2003), although the intrinsic excitability of neurons may also be altered (Farley et al, 1983;Cleary et al, 1998;Gainutdinov et al, 1998;Burrell et al, 2001;Antonov et al, 2001;Daoudal and Debanne, 2003;Zhang and Linden, 2003;Zhang et al, 2004). Remarkably, in the leech the ablation or axotomy of a single neuron, the S-cell, in just one ganglion eliminates a form of non-associative learning, sensitization of reflexive shortening (Sahley et al, 1994;Modney et al, 1997;Burrell et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Although S-cell firing is not required for reflexive shortening, following a sensitizing stimulus S-cells are more active, and more reliably so, during shortening in response to the test stimulus (Modney et al, 1997;Burrell et al, 2003). Both the capacity for sensitization and the increase in S-cell activity involve 5-HT (Ehrlich et al, 1992), which increases S-cell excitability (Burrell et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Neuronal competition for action potential initiation sites in a circuit controlling simple learning

2007

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The spatial and temporal patterns of action potential initiations were studied in a behaving leech preparation to determine the basis of increased firing that accompanies sensitization, a form of nonassociative learning requiring the S-interneurons. Little is known at the network level about mechanisms of behavioral sensitization. The S-interneurons, one in each ganglion and linked by electrical synapses with both neighbors to form a chain, are interposed between sensory and motor neurons. In sensitized preparations the strength of shortening is related to S-cell firing, which itself is the result of impulses initiating in several S-cells. Because the S-cells, as independent initiation sites, all contribute to activity in the chain, it was hypothesized that during sensitization, increased multi-site activity increased the chain's firing rate. However, it was found that during sensitization, the single site with the largest initiation rate, the S-cell in the stimulated segment, suppressed initiations in adjacent ganglia. Experiments showed this was both because (1) it received the earliest, greatest input and (2) the delayed synaptic input to the adjacent S-cells coincided with the action potential refractory period. A compartmental model of the S-cell and its inputs showed that a simple, intrinsic mechanism of inexcitability after each action potential may account for suppression of impulse initiations. Thus, a non-synaptic competition between neurons alters synaptic integration in the chain. In one mode, inputs to different sites sum independently, whereas in another, synaptic input to a single site precisely specifies the overall pattern of activity.

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Progressive recovery of learning during regeneration of a single synapse in the medicinal leech

Cited by 30 publications

References 44 publications

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

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

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

Neuronal competition for action potential initiation sites in a circuit controlling simple learning

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