Nicholas P. Vyleta

Bio: Nicholas P. Vyleta is an academic researcher from University of British Columbia. The author has contributed to research in topics: Long-term potentiation & Perforant path. The author has an hindex of 1, co-authored 2 publications receiving 2 citations.

Prolonged development of long-term potentiation at lateral entorhinal cortex synapses onto adult-born neurons.

Abstract: Critical period plasticity at adult-born neuron synapses is widely believed to contribute to the learning and memory functions of the hippocampus. Experience regulates circuit integration and for a transient interval, until cells are ~6 weeks old, new neurons display enhanced long-term potentiation (LTP) at afferent and efferent synapses. Since neurogenesis declines substantially with age, this raises questions about the extent of lasting plasticity offered by adult-born neurons. Notably, however, the hippocampus receives sensory information from two major cortical pathways. Broadly speaking, the medial entorhinal cortex conveys spatial information to the hippocampus via the medial perforant path (MPP), and the lateral entorhinal cortex, via the lateral perforant path (LPP), codes for the cues and items that make experiences unique. While enhanced critical period plasticity at MPP synapses is relatively well characterized, no studies have examined long-term plasticity at LPP synapses onto adult-born neurons, even though the lateral entorhinal cortex is uniquely vulnerable to aging and Alzheimer's pathology. We therefore investigated LTP at LPP inputs both within (4-6 weeks) and beyond (8+ weeks) the traditional critical period. At immature stages, adult-born neurons did not undergo significant LTP at LPP synapses, and often displayed long-term depression after theta burst stimulation. However, over the course of 3-4 months, adult-born neurons displayed increasingly greater amounts of LTP. Analyses of short-term plasticity point towards a presynaptic mechanism, where transmitter release probability declines as cells mature, providing a greater dynamic range for strengthening synapses. Collectively, our findings identify a novel form of new neuron plasticity that develops over an extended interval, and may therefore be relevant for maintaining cognitive function in aging.

Prolonged development of long-term potentiation at lateral entorhinal cortex synapses onto adult-born neurons

Abstract: Critical period plasticity at adult-born neuron synapses is widely believed to contribute to the learning and memory functions of the hippocampus. Experience regulates circuit integration and for a transient interval, until cells are ~6 weeks old, new neurons display enhanced long-term potentiation (LTP) at afferent and efferent synapses. Since neurogenesis declines substantially with age, this raises questions about the extent of lasting plasticity offered by adult-born neurons. Notably, however, the hippocampus receives sensory information from two major cortical pathways. Broadly speaking, the medial entorhinal cortex conveys spatial information to the hippocampus via the medial perforant path (MPP), and the lateral entorhinal cortex, via the lateral perforant path (LPP), codes for the cues and items that make experiences unique. While enhanced critical period plasticity at MPP synapses is relatively well characterized, no studies have examined long-term plasticity at LPP synapses onto adult-born neurons, even though the lateral entorhinal cortex is uniquely vulnerable to aging and Alzheimer’s pathology. We therefore investigated LTP at LPP inputs both within (4-6 weeks) and beyond (8+ weeks) the traditional critical period. At immature stages, adult-born neurons did not undergo significant LTP at LPP synapses, and often displayed long-term depression after theta burst stimulation. However, over the course of 3-4 months, adult-born neurons displayed increasingly greater amounts of LTP. Analyses of short-term plasticity point towards a presynaptic mechanism, where transmitter release probability declines as cells mature, providing a greater dynamic range for strengthening synapses. Collectively, our findings identify a novel form of new neuron plasticity that develops over an extended interval, and may therefore be relevant for maintaining cognitive function in aging.

The temporal origin of dentate granule neurons dictates their role in spatial memory.

Abstract: The dentate gyrus is one of the only brain regions that continues its development after birth in rodents. Adolescence is a very sensitive period during which cognitive competences are programmed. We investigated the role of dentate granule neurons (DGNs) born during adolescence in spatial memory and compared them with those generated earlier in life (in embryos or neonates) or during adulthood by combining functional imaging, retroviral and optogenetic tools to tag and silence DGNs. By imaging DGNs expressing Zif268, a proxy for neuronal activity, we found that neurons generated in adolescent rats (and not embryos or neonates) are transiently involved in spatial memory processing. In contrast, adult-generated DGNs are recruited at a later time point when animals are older. A causal relationship between the temporal origin of DGNs and spatial memory was confirmed by silencing DGNs in behaving animals. Our results demonstrate that the emergence of spatial memory depends on neurons born during adolescence, a function later assumed by neurons generated during adulthood.

Five discoveries of Volodymyr Betz. Part one. Betz and the islands of entorhinal cortex

Abstract: in the series of publications, which this article opens, we consider five fundamental neuromorphological observations of our compatriot, the classic of world neuroscience, Volodymr Betz. For four of them, we demonstrate the status of discoveries for the first time, for the other one — the giant pyramidal neurons of the motor cortex — despite its widespread and long-standing recognition, we reveal the limitations of modern knowledge and ideas. Two of the mentioned observations — giant fusiform, or spindle-shaped neurons of the cingulate and insular cortex and islands of the entorhinal cortex — are currently known only to a narrow circle of specialists; to the others two, islands of Calleja and signs of the columnar cortex organization, we pay attention for the first time. In this, the initial part of the series, exposing modern apprehensions about the structure and functions of the entorhinal cortex, we demonstrate the weight of Betz's pioneering observation of extraordinary neuron clusters, which are nowadays known as entorhinal islands, and prove the fact of recognizing his historical priority in the description of these amazing brain structures.

Somatic disinhibition of granule cells improves information transmission and pattern separation in the dentate gyrus

Abstract: Cortical circuits operate in a tight excitation/inhibition balance. This balance is relaxed during learning processes, but neither the mechanism nor its impact on network operations are well understood. In the present study, we combined in-vivo and in-vitro neuronal recordings with computational modelling and demonstrated that synaptic plasticity in the afferents from the entorhinal cortex (EC) to the dentate gyrus (DG), in addition to strengthening the glutamatergic inputs into granule cells (GCs), depressed perisomatic inhibition. Computational modelling revealed a functional reorganization in the inhibitory network that explained several experimental findings, including depression of the feed-forward inhibition. In vitro results confirmed a perisomatic dominance of the inhibitory regulation with important functional consequences. It favoured GCs burst firing, improved reliability of input/output transformations and enhanced separation and transmission of temporal and spatial patterns in the EC-DG-CA3 network.