Biomedical subjects

I Meilijson

Publications and source records attributed to I Meilijson.

5 recordsLinked to original sources

PubMed1999

Neuronal regulation: A mechanism for synaptic pruning during brain maturation.

Human and animal studies show that mammalian brains undergo massive synaptic pruning during childhood, losing about half of the synapses by puberty. We have previously shown that maintaining the network performance while synapses are deleted requires that synapses be properly modified and pruned, with the weaker synapses removed. We now show that neuronal regulation, a mechanism recently observed to maintain the average neuronal input field of a postsynaptic neuron, results in a weight-dependent synaptic modification. Under the correct range of the degradation dimension and synaptic upper bound, neuronal regulation removes the weaker synapses and judiciously modifies the remaining synapses. By deriving optimal synaptic modification functions in an excitatory-inhibitory network, we prove that neuronal regulation implements near-optimal synaptic modification and maintains the performance of a network undergoing massive synaptic pruning. These findings support the possibility that neural regulation complements the action of Hebbian synaptic changes in the self-organization of the developing brain.

Aging↗

PubMed1998

Synaptic pruning in development: a computational account.

Research with humans and primates shows that the developmental course of the brain involves synaptic overgrowth followed by marked selective pruning. Previous explanations have suggested that this intriguing, seemingly wasteful phenomenon is utilized to remove, "erroneous" synapses. We prove that this interpretation is wrong if synapses are Hebbian. Under limited metabolic energy resources restricting the amount and strength of synapses, we show that memory performance is maximized if synapses are first overgrown and then pruned following optimal "minimal-value" deletion. This optimal strategy leads to interesting insights concerning childhood amnesia.

Animals↗

PubMed1996

Simultaneously recorded single units in the frontal cortex go through sequences of discrete and stable states in monkeys performing a delayed localization task.

To test whether spiking activity of six to eight simultaneously recorded neurons in the frontal cortex of a monkey can be characterized by a sequence of discrete and stable states, neuronal activity is analyzed by a hidden Markov model (HMM). Using the HMM method, we are able to detect distinct states of neuronal activity within which firing rates are approximately stationary. Transitions between states, as expressed by concomitant changes in the firing rates of several units, occur quite abruptly. The significance and consistency of the states are confirmed by comparison with simulated data. The detected states are specific to a monkey's response in a delayed localization task, allowing correct prediction of the response in approximately 90% of the trials. Similar predictive power is achieved by a model based simply on the response histograms (PSTH) of the units. The two models reach this predictive ability with different time courses: the PSTH model gains predictive power with a higher rate in the first second of the delay, and the HMM gains predictive power with higher rate in the next 3 sec. In this later period, conventional methods such as the PSTH cannot detect any firing rate modulations, but the HMM successfully captures transitions between distinct states that are specific to the monkey's behavioral response and occur at highly variable times from trial to trial. Our results suggest that neuronal activity in this later period is described best as transitions among distinct states that may reflect discrete steps in the monkey's mental processes.

Animals↗

PubMed1995

Cortical activity flips among quasi-stationary states.

Parallel recordings of spike trains of several single cortical neurons in behaving monkeys were analyzed as a hidden Markov process. The parallel spike trains were considered as a multivariate Poisson process whose vector firing rates change with time. As a consequence of this approach, the complete recording can be segmented into a sequence of a few statistically discriminated hidden states, whose dynamics are modeled as a first-order Markov chain. The biological validity and benefits of this approach were examined in several independent ways: (i) the statistical consistency of the segmentation and its correspondence to the behavior of the animals; (ii) direct measurement of the collective flips of activity, obtained by the model; and (iii) the relation between the segmentation and the pair-wise short-term cross-correlations between the recorded spike trains. Comparison with surrogate data was also carried out for each of the above examinations to assure their significance. Our results indicated the existence of well-separated states of activity, within which the firing rates were approximately stationary. With our present data we could reliably discriminate six to eight such states. The transitions between states were fast and were associated with concomitant changes of firing rates of several neurons. Different behavioral modes and stimuli were consistently reflected by different states of neural activity. Moreover, the pair-wise correlations between neurons varied considerably between the different states, supporting the hypothesis that these distinct states were brought about by the cooperative action of many neurons.

Animals↗

PubMed1991

Maturation of the humoral immune response as an optimization problem.

Efficient immune response often depends on the production of high affinity antibodies. We show analytically that the optimal strategy for a fast production of high affinity antibodies is to utilize a step-function mutation rate, i.e. a minimal mutation rate in early stages of the immune response, followed by a discontinuous switch to the maximal possible rate when the proliferating population of B-cells exceeds a threshold value. Our results are in accordance with the biological observations concerning the time of onset of the hypermutation process, and with the mutation rate during the later stages of the primary immune response. Indeed the hypermutation process plays a crucial role in responding to a prevailing pathogen at each round of immune response, and not only for coping with future infections. Moreover, as the effect of hypermutations is shown to be crucially dependent on the number of proliferating B-cells, its onset is not expected to depend on an external signal, but rather to be related to the clone's age. This suggests that the onset is host species specific, rather than pathogen specific. Another implication of the present results is that activation of hypermutations before the B-cell population has reached the critical size may impede the efficiency of the response.

Animals↗