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.

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.

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.

Perifolliculitis capitis abscedens et suffodiens in an 18-year-old Aboriginal Canadian patient: case report and review of the literature.

BACKGROUND: Perifolliculitis capitis abscedens et suffodiens (PCAS) is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. This condition often presents in males of African American origin. OBJECTIVE: This article describes the clinical presentation, diagnosis, and treatment of an Aboriginal Canadian male suffering from PCAS. A literature review on the etiology, pathology, differential diagnosis, and management is also discussed. CONCLUSION: Careful analysis of the pathology and clinical presentation can aid in the timely diagnosis and management of this challenging condition. The clinician dealing with patients suffering from PCAS has several treatment options available to help successfully manage patients with straightforward or recalcitrant disease.

Juvenile Lymnaea ventilate, learn and remember differently than do adult Lymnaea.

Adult snails are capable of learning associatively not to perform aerial respiration and then to consolidate the acquired behaviour into long-term memory (LTM). Juvenile Lymnaea, however, perform aerial respiration significantly less often and the three-neuron circuit that drives this behaviour operates significantly differently than in it does in adults. We asked whether these ontogenic behavioural and neurophysiological differences are manifested as an altered ability of juveniles to learn and/or form LTM. We found that juvenile snails learn significantly less well than adults and are, as a group, incapable of forming LTM. To control for the possibility that the poor learning and inability to form memory were the result of juvenile's receiving on average fewer reinforcing stimuli because they perform aerial respiration less often than adults we subjected juveniles to an enforced period of hypoxia to "motivate" juveniles. Motivated juveniles perform aerial respiration as often as adults; yet these "motivated" juveniles continue to be poor learners and still cannot form LTM. Additionally, a small percentage of juveniles perform aerial respiration as often as adults (i.e. high responders). When these "high-responders" were trained they still exhibited poorer learning ability compared with adults and could not form LTM. We conclude that juvenile snails have a more difficult time learning and remembering to suppress aerial respiratory activity than do adults.

Operant conditioning of an in vitro CNS-pneumostome preparation of Lymnaea.

Operant conditioning of aerial respiratory behaviour and its consolidation into long-term memory in Lymnaea has been previously studied in both intact, freely moving snails and in in vitro preparations made from previously trained snails. Here, we show in previously untrained semi-intact in vitro Lymnaea preparations that aerial respiratory behaviour can also be operantly conditioned. Neither yoked control nor 'run-down' control procedures in these in vitro preparations result in an alteration of aerial respiratory behaviour. Memory in the operantly trained semi-intact preparations persists for at least 1h after training. Intracellular recordings made from RPeD1, one of the 3-CPG neurons and the neuron that initiates CPG activity; show that there are specific changes in central excitatory input to this neuron concurrent with learning and its consolidation into memory. In addition following the acquisition of learning and its consolidation into memory the ability of RPeD1 and VI/J neurons when depolarized to cause a pneumostome opening is significantly decreased. Thus, previously untrained in vitro semi-intact preparations can be used to study changes in neuronal activity in a neuron known to be both necessary for the behaviour and for memory formation.

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.