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Biomedical subjects

Susan Sangha

Publications and source records attributed to Susan Sangha.

17 recordsLinked to original sources
PubMed2006

Modulation of aerial respiratory behaviour in a pond snail.

Aerial respiratory in Lymnaea is driven by a three-neuron CPG whose sufficiency and necessity has been directly demonstrated. While this CPG is 'hard-wired' it displays a tremendous amount of plasticity. That is, it is possible by employing specific training procedures to alter how it functions in a specific hypoxic environment. Thus, it is possible to study directly the causal mechanisms of long-term memory formation, forgetting, and modulation of the memory at a single cell level. Thus, it is possible to use a relatively simple three-neuron CPG to study not only important questions concerning regulation of important homeostatic mechanisms but to also use it to study how learning and non-declarative memory are mediated at a cellular level.

Animals↗
PubMed2005

Decreased sensory stimulation reduces behavioral responding, retards development, and alters neuronal connectivity in Caenorhabditis elegans.

Activity-dependent plasticity is a critical component of nervous systems. We show that in Caenorhabditis elegans, worms raised in isolation made smaller responses to mechanosensory stimulation and were smaller and slower to begin laying eggs than age-matched group-raised worms. The glutamate receptor gene GLR-1 was critical for the observed alterations in behavior but not in size, whereas the cGMP-dependent protein kinase gene EGL-4 was critical for the observed changes in size but not the changes in behavior. Mechanosensory stimulation during development reversed the effects of isolation on behavior and began to reduce the effects of isolation on size. In C. elegans, the six mechanosensory touch neurons synapse onto the four pair of command interneurons for forward and backward movement. Touch (mechanosensory) neurons of worms raised in isolation expressed lower levels of green fluorescent protein (GFP)-tagged synaptobrevin than touch neurons of worms raised in colonies. Command interneurons of worms raised in isolation expressed lower levels of GFP-tagged glutamate receptors than command interneurons of worms raised in groups. Brief mechanical stimulation during larval development rescued the expression of GFP-tagged glutamate receptors but not GFP-tagged synaptobrevin. Together, these results indicate that the level of stimulation experienced by C. elegans during development profoundly affects the development of neuronal connectivity and has widespread cellular and behavioral consequences.

Animals↗
PubMed2005

Impairing forgetting by preventing new learning and memory.

Two causes of forgetting have been promulgated: memory trace decay and retroactive interference. The authors show that forgetting is an active process requiring both new learning and memory. In the present (1)Lymnaea model system, prevention of new learning of a conflicting association, inhibition of memory consolidation, or Right Pedal Dorsal 1 soma ablation, which blocks LTM formation, are all potent means to prevent forgetting. Thus procedures that alter the ability to learn or form memory of a new conflicting aerial respiratory association prevent forgetting of a learned associative behavior. These results are the 1st demonstration in any model system that forgetting requires the soma of a single neuron.

Analysis of Variance↗
PubMed2005

Boosting intermediate-term into long-term memory.

Aerial respiration in the pond snail Lymnaea stagnalis can be operantly conditioned. Depending on the specific training procedure used (i.e. a 0.5 h vs a 1.0 h interval between training sessions) either intermediate (ITM) or long-term memory (LTM) is formed. ITM, which persists for 2-3 h, is dependent only on de novo protein synthesis, whilst LTM persists for up to 4 weeks and is dependent on both transcription and de novo protein synthesis. We found that although the behavioural phenotype of ITM was not apparent 24 h after the last training session, a residual memory trace was present that serves as a foundation upon which a subsequent ITM-training-procedure builds on to form LTM (i.e. a "changed memory"). This residual memory trace could be perturbed by cooling, the behavioural process of context-specific extinction and by increasing the interval between the training procedures. Furthermore in preparations where the somata of RPeD1 (one of three interneurons in the central pattern generator required for aerial respiratory behavior) had been ablated before training, LTM could not be observed following a second bout of ITM-training. These data support the concept that a molecular memory trace is established as a consequence of ITM-training, which serves as a "permissive substrate", when the ITM memory is made active, sufficient to permit the necessary transcription and translation processes that are causal for LTM formation.

Analysis of Variance↗
PubMed2004

Memory, reconsolidation and extinction in Lymnaea require the soma of RPeD1.

The central pattern generator (CPG) that drives aerial respiratory behaviour in Lymnaea consists of 3 neurons. One of these, RPeD1--the cell that initiates activity in the circuit, plays an absolutely necessary role as a site for memory formation, memory reconsolidation, and extinction. Using an operant conditioning training procedure that results in a long-term non-declarative memory (LTM), we decrease the occurrence of aerial respiratory behaviour. Since snails can still breathe cutaneously learning this procedure is not harmful. Concomitant with behavioural memory are changes in the spiking activity of RPeD1. Going beyond neural correlates of memory we directly show that RPeD1 is a necessary site for LTM formation. Expanding on this finding we show that this neuron is also a necessary site for memory reconsolidation and 'Pavlovian' extinction. As far as we can determine, this is the first time a single neuron has been shown to be a necessary site for these different aspects memory. RPeD1 is thus a key neuron mediating different hierarchical aspects of memory. We are now in a position to determine the necessary neuronal, molecular and proteomic events in this neuron that are causal to memory formation, reconsolidation and extinction.

Animals↗
PubMed2003

Extinction requires new RNA and protein synthesis and the soma of the cell right pedal dorsal 1 in Lymnaea stagnalis.

Lymnaea stagnalis were operantly conditioned to not perform aerial respiratory behavior. This learned response was subsequently extinguished. Here, we show that spaced extinction training is more effective than massed extinction training, in addition to the occurrence of spontaneous recovery. We also find evidence of a critical period within the first hour after extinction training in which new RNA and protein synthesis must occur for a memory of extinction training to be established. The memory for extinction training can also be extended using cooling and by preventing aerial respiration from occurring after extinction training. In addition, we demonstrate that memory formation of extinction training requires the soma of the cell right pedal dorsal 1, a cell that we have previously shown to be necessary for long-term memory consolidation and reconsolidation. This finding implies that the events that lead to the formation of extinction memory occur in the same cell that is responsible for long-term memory of operant conditioning. All of these data are consistent with the hypothesis that, during extinction, a new associative memory is being formed and that this new memory covers up, but does not abolish, the "old" memory.

Animals↗
PubMed2003

Reconsolidation of a long-term memory in Lymnaea requires new protein and RNA synthesis and the soma of right pedal dorsal 1.

Reconsolidation of a long-term memory (LTM) in the snail Lymnaea stagnalis can be disrupted by cooling, an RNA synthesis blocker (actinomycin D), and by specifically ablating the soma of a cell we know is a site of LTM consolidation (right pedal dorsal 1, RPeD1). Aerial respiratory behavior was conditioned operantly by applying a gentle tactile stimulus to the pneumostome area (the respiratory orifice) every time the snail began to open its pneumostome to perform aerial respiration. This resulted in a reduction of this behavior while leaving cutaneous respiration intact. One week after training one-half of the animals received a memory reactivation session, which was similar to the original training (i.e., animals received reinforcement). All animals then received 1 hr of cooling, an injection of actinomycin D or saline, or the soma ablation procedure. This was followed by a test for savings 4 hr or 4 d later, which was also similar to the original training. Only those animals that received both the memory reactivation session and the treatment showed memory impairment during the test for savings. That is, the impairment was contingent on memory reactivation. These data indicate that reconsolidation requires both new RNA and protein synthesis to stabilize a reactivated memory, and it demonstrates that the soma of RPeD1, a cell that we have shown previously to be required in the consolidation of an LTM, is necessary for reconsolidation. These data suggest that the critical molecular processes occurring during both consolidation and reconsolidation transpire in the same cell in Lymnaea.

Animals↗
PubMed2003

A molluscan model system in the search for the engram.

A 3-neuron central pattern generator, whose sufficiency and necessity has been directly demonstrated, mediates aerial respiratory behaviour in the pond snail, Lymnaea stagnalis. This behaviour can be operantly conditioned, and this associative learning is consolidated into long-lasting memory. Depending on the operant conditioning training procedure used the learning can be consolidated into intermediate term (ITM) or long-term memory (LTM). ITM persists for only 2-3 h, whilst LTM persists for days to weeks. LTM is dependent on both altered gene activity and new protein synthesis while ITM is only dependent on new protein synthesis. We have now directly established that one of the 3-CPG neurons, RPeD1, is a site of LTM formation and storage. We did this by ablating the soma of RPeD1 and leaving behind a functional primary neurite capable of mediating the necessary synaptic interactions to drive aerial respiratory behaviour by the 3-neuron CPG. However, following soma ablation the neuronal circuit is only capable of mediating learning and ITM. LTM can no longer be demonstrated. However, if RPeD1's soma is ablated after LTM consolidation memory is still present. Thus the soma is not needed for the retention of LTM. Using a similar strategy it may be possible to block forgetting.

Animals↗
PubMed2003

Cooling blocks ITM and LTM formation and preserves memory.

In Lymnaea aerial respiratory behaviour can be operantly conditioned; snails learn not to perform this behaviour. Depending on the training procedure used, snails are competent to form either intermediate-term (ITM; lasting 1-3 h) or long-term (LTM; >4 h) memory. We found that cooling the snails for 1 h immediately after training was sufficient to block either ITM or LTM. Cooling snails for a similar period 10 or 15 min after cessation of training, failed to block ITM and LTM formation, respectively. Finally, we employed the cooling technique to extend both ITM and LTM. That is, cooling could prevent forgetting. Cooling extended LTM that normally persisted for 2 days to at least 8 days. These data are consistent with the hypothesis that forgetting is due to the learning and remembering of interfering events, and thus is an active process.

Animals↗
PubMed2003

Forgetting and the extension of memory in Lymnaea.

Aerial respiratory behaviour in Lymnaea stagnalis was operantly conditioned using a procedure that results in long-term memory (LTM) persisting for 1 but not 3 days. By manipulating the snails' post-training environment, i.e. preventing Lymnaea from performing aerial respiratory behaviour, memory persistence was significantly extended. Memory retention, however, is only extended if snails are prevented from performing aerial respiration in the same context in which they were trained. Snails trained in the 'standard' context but prevented from performing aerial respiration in the 'carrot-odor' context (and vice versa) did not extend their memory. These data are consistent with the hypothesis that forgetting is due to interfering events, that occur following learning and memory consolidation.

Animals↗
PubMed2003

Intermediate and long-term memories of associative learning are differentially affected by transcription versus translation blockers in Lymnaea.

Aerial respiratory behaviour in the pond snail, Lymnaea stagnalis, can be operantly conditioned. This associative learning then undergoes consolidation into a long-lasting memory which, depending on the training procedure used, causes intermediate-term memory (ITM; lasting 3 h) or long-term memory (LTM; lasting >6 h) to be formed. We determined the differential susceptibility of these two forms of memory to translation and transcription blockers. The injection of a translation blocker, Anisomycin, 2.5 h before training prevents the establishment of both ITM and LTM. On the other hand, injection of the transcription blocker Actinomycin D, 2.5 h before training, did not prevent the establishment of ITM, but did, however, prevent LTM formation. Thus in Lymnaea, following associative learning, both ITM and LTM are dependent on new protein synthesis. ITM appears to be dependent on protein synthesis from preexisting transcription factors, whilst LTM is dependent on protein synthesis from new transcription messages.

Animals↗
PubMed2003

Associative learning and memory in Lymnaea stagnalis: how well do they remember?

The search for 'the how and the where' of memory formation in the brain, the engram, is still one of the unattained 'Holy Grails' of neuroscience. Over the years, various paths have been trodden in attempts to attain this goal, and while tantalizing glimpses appear now and then on the scientific horizon, the Grail still has not been grasped. One of the paths that investigators have walked is the invertebrate 'model system' approach. Some invertebrates possess relatively simple nervous systems that mediate relatively simple behaviours that are both interesting and trainable. In this commentary, we would like to shed light on a relatively new player, the pond snail Lymnaea stagnalis L., that is being used in the quest to illuminate 'the how and the where' the nervous systems encode and store memory. We will show that it is possible to demonstrate that a single neuron is a site of memory formation and storage for a form of associative learning in this lowly snail. It may be that the Grail is a little closer to being grasped.

Animals↗
PubMed2002

Context extinction and associative learning in Lymnaea.

Aerial respiratory behavior in the pond snail Lymnaea was operantly conditioned so that snails learned not to perform aerial respiration in a hypoxic environment. Snails were trained in either the standard context (no food odorant) or a carrot (food-odorant) context. An operant training procedure of two 45-min training sessions with a 1-h interval between the sessions followed by a third 45-min training session 18 h later was sufficient to produce associative learning and long-term memory (LTM) that persisted for at least 5 days. If, however, following the third operant training session snails received three 45-min extinction training sessions, with each extinction session separated by at least a 1-h interval, LTM was not observed when tested the following day. That is, the memory was extinguished. Extinction, however, did not occur if the context of the extinction training was different from the context of the associative training. That is, in the snails trained in the standard context, extinction did not occur if the extinction training sessions were performed in the food-odorant context and vice versa.

Animals↗
PubMed2002

Gone but not forgotten: the lingering effects of intermediate-term memory on the persistence of long-term memory.

Aerial respiratory behaviour can be operantly conditioned in Lymnaea stagnalis and, depending on the interval between the training sessions, memories of significantly different durations are produced. In naïve snails, a 15 min training procedure with a 30 min interval between three training sessions results in memory that persists for only 3 h (intermediate-term memory, ITM); whilst if the three 15 min training sessions are separated by a 1 h interval memory persists for 48 h (long-term memory, LTM). We found that if ITM training preceded LTM training, then LTM would persist for 24 h longer. This augmenting effect on LTM persistence could be demonstrated for up to 5 h following the last ITM training session, even though ITM was not observed at that time. However, if LTM training ensued 8 h after the last ITM training session, an augmented LTM did not occur. Extinguishing the memory produced by the ITM training procedure also prevented augmentation of LTM. That is, if an extinction procedure was given to the snails after the ITM training procedure, LTM did not persist longer than 48 h. Thus, at the behavioural level, ITM and LTM are interconnected.

Animals↗
PubMed2002

The effects of continuous versus partial reinforcement schedules on associative learning, memory and extinction in Lymnaea stagnalis.

A continuous schedule of reinforcement (CR) in an operant conditioning procedure results in the acquisition of associative learning and the formation of long-term memory. A 50 % partial reinforcement (PR) schedule does not result in learning. The sequence of PR-CR training has different and significant effects on memory retention and resistance to extinction. A CR/PR schedule results in a longer-lasting memory than a PR/CR schedule. Moreover, the memory produced by the CR/PR schedule is resistant to extinction training. In contrast, extinction occurs following the PR/CR schedule.

Animals↗
PubMedDate not supplied

Long-term memory survives nerve injury and the subsequent regeneration process.

A three-neuron network (a central pattern generator [CPG]) is both sufficient and necessary to generate aerial respiratory behavior in the pond snail, Lymnaea stagnalis. Aerial respiratory behavior is abolished following a specific nerve crush that results in axotomy to one of the three CPG neurons, RPeD1. Functional regeneration of the crushed neurite occurs within 10 days, allowing aerial respiratory behavior to be restored. Functional regeneration does not occur if the connective is cut rather than crushed. In unaxotomized snails, aerial respiratory behavior can be operantly conditioned, and following memory consolidation, long-term memory (LTM) persists for at least 2 weeks. We used the Lymnaea model system to determine (1) If in naive animals axotomy and the subsequent regeneration result in a nervous system that is competent to mediate associative learning and LTM, and (2) if LTM survives RPeD1 axotomy and the subsequent regenerative process. We show here that (1) A regenerated nervous system is competent to mediate associative memory and LTM, and (2) LTM survives axotomy and the subsequent regenerative process.

Animals↗