Synaptic Traces Research Articles

Intrinsic Projections of Layer Vb Neurons to Layers Va, III, and II in the Lateral and Medial Entorhinal Cortex of the Rat

Layer V of the entorhinal cortex (EC) receives input from the hippocampus and originates main entorhinal outputs. The deep-sublayer Vb, immunopositive for the transcription factor Ctip2, is thought to be the main recipient of hippocampal projections, whereas the superficial-sublayer LVa, immunonegative for Ctip2, originates the main outputs of EC. This disrupts the proposed role of EC as mediating hippocampal-cortical interactions. With the use of specific (trans)synaptic tracing approaches, we report that, in medial entorhinal cortex, layer Vb neurons innervate neurons in layers Va, II, and III. A similar circuitry exists in the lateral entorhinal cortex. We conclude that EC-layer Vb neurons mediate two circuits in the hippocampus-memory system: (1) a hippocampal output circuit to telencephalic areas by projecting to layer Va and (2) a feedback projection, sending information back to the EC-hippocampal loop via neurons in layers II and III.

Receptor-mediated increase in rabies virus axonal transport.

Rabies virus (RABV) of the rhabdoviridae family is a prototype neurotropic virus that causes a fatal disease, and is still a major risk mostly in developing countries. A key step in the RABV infection process is its arrival into the central nervous system (CNS), for which it uses the cellular transport machinery. Neurons are irregular cells with a specialized anatomy, and often extend lengthy axons that may span over a meter long. In infected organisms, RABV virions enter the neuron periphery at the area of a bite and must overcome great distances in order to reach the peripheral neuron's cell body and from there, the CNS. To this end, RABV exploits the retrograde axonal transport machinery, a fast and directed route aimed for trafficking cargo from the neuron periphery to its soma. RABV's neuronal tropism and retrograde propagation, combined with the development of safe, labeled viruses in recent years (Klingen et al., 2008), have rendered it ideal for neural and synaptic tracing.

Analysis of memory consolidation and evocation in rats by proton induced X-ray emission

It is well known that trace elements such as Mg, Ca, Fe, Cu and Zn have a key role in synapse plasticity and learning. Learning process is conventionally divided in three distinct and complementary stages: memory acquisition, consolidation and evocation. Consolidation is the stabilization of the synaptic trace formed by acquisition, while evocation is the recall of this trace. Ion-based techniques capable of providing information concerning the elemental composition of organic tissues may be helpful to improve our understanding on memory consolidation and evocation processes. In particular, the Particle-Induced X-ray Emission (PIXE) technique can be used to analyze different biological tissues with good accuracy. In this work we explore the versatility of PIXE to measure the elemental concentrations in rat brain tissues in order to establish any possible correlation between them and the memory consolidation and evocation processes. To this end, six groups of middle-age male Wistar rats were trained and tested in a step-down Inhibitory Avoidance conditioning. After the behavior tests, the animals were decapitated in accordance with the legal procedures and their brains were removed and dissected for the PIXE analyses. The results demonstrated that there are differences in the elemental concentration among the groups and such variations may be associated with their availability to the learning processes (by memory consolidation and evocation). Moreover, the control groups circumvent the possibility that a non-specific event involved in learning tasks cause such variations. Our results suggest that PIXE may be a useful tool to investigate memory consolidation and evocation in animal models.

A theory for how sensorimotor skills are learned and retained in noisy and nonstationary neural circuits

During the process of skill learning, synaptic connections in our brains are modified to form motor memories of learned sensorimotor acts. The more plastic the adult brain is, the easier it is to learn new skills or adapt to neurological injury. However, if the brain is too plastic and the pattern of synaptic connectivity is constantly changing, new memories will overwrite old memories, and learning becomes unstable. This trade-off is known as the stability-plasticity dilemma. Here a theory of sensorimotor learning and memory is developed whereby synaptic strengths are perpetually fluctuating without causing instability in motor memory recall, as long as the underlying neural networks are sufficiently noisy and massively redundant. The theory implies two distinct stages of learning--preasymptotic and postasymptotic--because once the error drops to a level comparable to that of the noise-induced error, further error reduction requires altered network dynamics. A key behavioral prediction derived from this analysis is tested in a visuomotor adaptation experiment, and the resultant learning curves are modeled with a nonstationary neural network. Next, the theory is used to model two-photon microscopy data that show, in animals, high rates of dendritic spine turnover, even in the absence of overt behavioral learning. Finally, the theory predicts enhanced task selectivity in the responses of individual motor cortical neurons as the level of task expertise increases. From these considerations, a unique interpretation of sensorimotor memory is proposed--memories are defined not by fixed patterns of synaptic weights but, rather, by nonstationary synaptic patterns that fluctuate coherently.

Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb

Identifying the connectome of adult-generated neurons is essential for understanding how the preexisting circuitry is refined by neurogenesis. Changes in the pattern of connectivity are likely to control the differentiation process of newly generated neurons and exert an important influence on their unique capacity to contribute to information processing. Using a monosynaptic rabies virus-based tracing technique, we studied the evolving presynaptic connectivity of adult-generated neurons in the dentate gyrus (DG) of the hippocampus and olfactory bulb (OB) during the first weeks of their life. In both neurogenic zones, adult-generated neurons first receive local connections from multiple types of GABAergic interneurons before long-range projections become established, such as those originating from cortical areas. Interestingly, despite fundamental similarities in the overall pattern of evolution of presynaptic connectivity, there were notable differences with regard to the development of cortical projections: although DG granule neuron input originating from the entorhinal cortex could be traced starting only from 3 to 5 wk on, newly generated neurons in the OB received input from the anterior olfactory nucleus and piriform cortex already by the second week. This early glutamatergic input onto newly generated interneurons in the OB was matched in time by the equally early innervations of DG granule neurons by glutamatergic mossy cells. The development of connectivity revealed by our study may suggest common principles for incorporating newly generated neurons into a preexisting circuit.

CHALLENGING THE WORKING MEMORY MODEL OF THOUGHT ABSTRACTION

Working memory, the ability to keep recently accessed information available for immediate manipulation, has been proposed to rely on two mechanisms that appear difficult to reconcile: self-sustained neural firing, or the opposite—activity-silent synaptic traces. Here we review and contrast models of these two mechanisms, and then show that both phenomena can co-exist within a unified system in which neurons hold information in both activity and synapses. Rapid plasticity in flexibly-coding neurons allows features to be bound together into objects, with an important emergent property being the focus of attention. One memory item is held by persistent activity in an attended or “focused” state, and is thus remembered better than other items. Other, previously attended items can remain in memory but in the background, encoded in activity-silent synaptic traces. This dual functional architecture provides a unified common mechanism accounting for a diversity of perplexing attention and memory effects that have been hitherto difficult to explain in a single theoretical framework.

Sequence learning in differentially activated dendrites

Differentially activated areas of a dendrite permit the existence of zones with distinct rates of synaptic modification, and such areas can be individually accessed using a reference signal which localizes synaptic plasticity and memory trace retrieval to certain subregions of the dendrite. It is proposed that the neural machinery required in such a learning/retrieval mechanism could involve the NMDA receptor, in conjunction with the ability of dendrites to maintain differentially activated regions. In particular, it is suggested that such a parcellation of the dendrite allows the neuron to participate in multiple sequences, which can be learned without suffering from the ‘wash-out’ of synaptic efficacy associated with superimposition of training patterns. This is a biologically plausible solution to the stability–plasticity dilemma of learning in neural networks.