Differential effects of electrical stimulation patterns, motivational-behavioral stimuli and their order of application on functional plasticity processes within one input in the dentate gyrus of freely moving rats in vivo.

Hippocampal long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy considered to be the cellular basis of memory. LTP consists of an early, protein synthesis-independent phase (E-LTP) and a late phase that depends on protein synthesis (L-LTP). In water-deprived rats E-LTP in the dentate gyrus (DG) can be reinforced into L-LTP, if the rats were allowed to drink within 15 min after E-LTP induction (behavioral LTP-reinforcement, BR). LTP can be depotentiated by low-frequency stimulation (LFS) to the same synaptic input if applied shortly after tetanization (<10 min). Here, we addressed the question of whether a BR protocol is able to recover LTP at depotentiated synaptic inputs. We show that LTP, depotentiation, LFS and BR specifically interact within one afferent input, which could be explained by the "synaptic tagging" hypothesis outlined by [Frey and Morris (1997) Nature 385:533-536]. E-LTP induced by a weak tetanus (WTET) sets tags in the activated inputs which are able to capture and to process plasticity-related proteins (PRPs) required for L-LTP, the synthesis of which was induced by BR. Synaptic tags could be reset by LFS. BR alone was unable to rescue depotentiated LTP, but the combination of BR and subsequent WTET transformed E-LTP into L-LTP. We show that LTP, LTD and behavioral stimuli alternatively and reversibly affect a single afferent input for long periods of time by LTP as well as LTD mechanisms, competing with each other under the influence of different concurrent stimuli. Affective modulation can shift the balance to one or the other. We show that the result will depend not only on the last stimulus, but on the history of previous stimuli applied to the specific input. Afferent stimuli activate alternative, but partially overlapping cascades with long-lasting consequences for the input including spaced-associative processes of "synaptic tagging" as well as "cross-tagging" which could be demonstrated in single synaptic afferents to one neuronal population in freely behaving animals.

[Synaptic tagging and memory trace]. / La 'marca sinaptica' y la huella de la memoria.

AIM: To present a panorama of the main features and possible identity of the synaptic tag, such as to discuss some of its functional implications. DEVELOPMENT: Long-term potentiation (LTP) constitutes a very attractive synaptic/cellular memory model. LTP, like memory, can manifest itself early (essentially depending on the modification of pre-existing proteins at synapse) and late (depending on new protein synthesis). As LTP is a highly specific phenomenon, a dilemma arises: how can the proteins, required to plastic change stabilization, that are synthesized at the soma of a neuron containing thousands of synaptic contacts--all depending of the same nucleus--go to the appropriate synapses? In this review, we present some of the models that intend to explain this question, making emphasis on synaptic tagging hypothesis. Some of the main findings that have contributed to tagging hypothesis are exposed. The local protein synthesis and the activation of protein kinases are analyzed as candidates to be the synaptic tag. Additionally, some of the functional implications of synaptic tagging are discussed. CONCLUSIONS: The synaptic tagging hypothesis offers a very flexible and reasonable solution to the specificity of long-lasting synaptic changes. Although some of the tagging features are known, the synaptic tag identity has not yet been elucidated. It seems that there is not a unique synaptic tag, but there are rather multiple molecular synaptic tags involved. Each of them might function as a synaptic tag under particular circumstances. Each might be differentially recruited by specific stimuli and mediate plasticity over different time domains.

La ‘marca sináptica’ y la huella de la memoriar / Synaptic tagging and memory trace

Presentar una visión de las principales características y posible identidad de la marca sináptica, así comodiscutir algunas de sus implicaciones funcionales. Desarrollo. La potenciación sináptica a largo plazo, dadas sus características, se ha impuesto como un modelo sinapticocelular de memoria muy atractivo. De modo similar a la memoria, puede manifestarse como temprana (dependiente fundamentalmente de la modificación de proteínas preexistentes en la sinapsis) otardía (dependiente de la síntesis de nuevas proteínas). Debido a que la potenciación sináptica a largo plazo es un fenómeno altamente específico, surge un dilema: ¿cómo llegan a las sinapsis apropiadas las proteínas requeridas para la estabilizacióndel cambio plástico en una neurona que normalmente posee miles de contactos sinápticos, todos dependientes del mismo núcleo? En este trabajo se presentan algunos de los modelos que aportan posibles soluciones a este interrogante, haciendo énfasisen la hipótesis del marcaje sináptico. Se exponen los principales hallazgos que han ido conformando esta hipótesis y se analiza la síntesis local y la activación de proteincinasas como posibles candidatos de ser la marca sináptica. Adicionalmente, sediscuten algunas implicaciones funcionales del marcaje sináptico. Conclusiones. La hipótesis de la marca sináptica ofrece una explicación muy flexible y razonable acerca de la especificidad del cambio sináptico duradero. Aunque se conocen algunas desus características, la identidad de la marca no se ha dilucidado aún. Al parecer, existen múltiples marcas que, al ser reclutadas por estímulos específicos, median los efectos plásticos en diferentes dominios temporales

To present a panorama of the main features and possible identity of the synaptic tag, such as to discuss someof its functional implications. Development. Long-term potentiation (LTP) constitutes a very attractive synaptic/cellular memory model. LTP, like memory, can manifest itself early (essentially depending on the modification of pre-existing proteins atsynapse) and late (depending on new protein synthesis). As LTP is a highly specific phenomenon, a dilemma arises: how can the proteins, required to plastic change stabilization, that are synthesized at the soma of a neuron containing thousands ofsynaptic contacts –all depending of the same nucleus– go to the appropriate synapses? In this review, we present some of the models that intend to explain this question, making emphasis on synaptic tagging hypothesis. Some of the main findings that have contributed to tagging hypothesis are exposed. The local protein synthesis and the activation of protein kinases areanalyzed as candidates to be the synaptic tag. Additionally, some of the functional implications of synaptic tagging are discussed. Conclusions. The synaptic tagging hypothesis offers a very flexible and reasonable solution to the specificity oflong-lasting synaptic changes. Although some of the tagging features are known, the synaptic tag identity has not yet been elucidated. It seems that there is not a unique synaptic tag, but there are rather multiple molecular synaptic tags involved.Each of them might function as a synaptic tag under particular circumstances. Each might be differentially recruited by specific stimuli and mediate plasticity over different time domains

La marca sináptica y la huella de la memoria / Synaptic tagging and memory trace

Objetivo. Presentar una visión de las principales características y posible identidad de la marca sináptica, así comodiscutir algunas de sus implicaciones funcionales. Desarrollo. La potenciación sináptica a largo plazo, dadas sus características, se ha impuesto como un modelo sinapticocelular de memoria muy atractivo. De modo similar a la memoria, puede manifestarse como temprana (dependiente fundamentalmente de la modificación de proteínas preexistentes en la sinapsis) otardía (dependiente de la síntesis de nuevas proteínas). Debido a que la potenciación sináptica a largo plazo es un fenómeno altamente específico, surge un dilema: ¿cómo llegan a las sinapsis apropiadas las proteínas requeridas para la estabilizacióndel cambio plástico en una neurona que normalmente posee miles de contactos sinápticos, todos dependientes del mismo núcleo? En este trabajo se presentan algunos de los modelos que aportan posibles soluciones a este interrogante, haciendo énfasisen la hipótesis del marcaje sináptico. Se exponen los principales hallazgos que han ido conformando esta hipótesis y se analiza la síntesis local y la activación de proteincinasas como posibles candidatos de ser la marca sináptica. Adicionalmente, se discuten algunas implicaciones funcionales del marcaje sináptico. Conclusiones. La hipótesis de la marca sináptica ofrece unaexplicación muy flexible y razonable acerca de la especificidad del cambio sináptico duradero. Aunque se conocen algunas de sus características, la identidad de la marca no se ha dilucidado aún. Al parecer, existen múltiples marcas que, al ser reclutadaspor estímulos específicos, median los efectos plásticos en diferentes dominios temporales(AU)

AIM: To present a panorama of the main features and possible identity of the synaptic tag, such as to discuss some of its functional implications. DEVELOPMENT: Long-term potentiation (LTP) constitutes a very attractive synaptic/cellular memory model. LTP, like memory, can manifest itself early (essentially depending on the modification of pre-existing proteins at synapse) and late (depending on new protein synthesis). As LTP is a highly specific phenomenon, a dilemma arises: how can the proteins, required to plastic change stabilization, that are synthesized at the soma of a neuron containing thousands of synaptic contacts--all depending of the same nucleus--go to the appropriate synapses? In this review, we present some of the models that intend to explain this question, making emphasis on synaptic tagging hypothesis. Some of the main findings that have contributed to tagging hypothesis are exposed. The local protein synthesis and the activation of protein kinases are analyzed as candidates to be the synaptic tag. Additionally, some of the functional implications of synaptic tagging are discussed. CONCLUSIONS: The synaptic tagging hypothesis offers a very flexible and reasonable solution to the specificity of long-lasting synaptic changes. Although some of the tagging features are known, the synaptic tag identity has not yet been elucidated. It seems that there is not a unique synaptic tag, but there are rather multiple molecular synaptic tags involved. Each of them might function as a synaptic tag under particular circumstances. Each might be differentially recruited by specific stimuli and mediate plasticity over different time domains(AU)