OBJECTIVE: One of the primary goals of neuroscience is to understand how neurons encode and process information about their environment. The problem is often approached indirectly by examining the degree to which the neuronal response reflects the stimulus feature of interest. APPROACH: In this context, the methods of signal estimation and detection theory provide the theoretical limits on the decoding accuracy with which the stimulus can be identified. The Cramér-Rao lower bound on the decoding precision is widely used, since it can be evaluated easily once the mathematical model of the stimulus-response relationship is determined. However, little is known about the behavior of different decoding schemes with respect to the bound if the neuronal population size is limited. MAIN RESULTS: We show that under broad conditions the optimal decoding displays a threshold-like shift in performance in dependence on the population size. The onset of the threshold determines a critical range where a small increment in size, signal-to-noise ratio or observation time yields a dramatic gain in the decoding precision. SIGNIFICANCE: We demonstrate the existence of such threshold regions in early auditory and olfactory information coding. We discuss the origin of the threshold effect and its impact on the design of effective coding approaches in terms of relevant population size.

• MeSH
• akční potenciály fyziologie   MeSH
• algoritmy * MeSH
• evokované potenciály fyziologie   MeSH
• lidé MeSH
• modely neurologické * MeSH
• neurony fyziologie   MeSH
• percepce fyziologie   MeSH
• počítačová simulace MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

Information theory quantifies the ultimate limits on reliable information transfer by means of the channel capacity. However, the channel capacity is known to be an asymptotic quantity, assuming unlimited metabolic cost and computational power. We investigate a single-compartment Hodgkin-Huxley type neuronal model under the spike-rate coding scheme and address how the metabolic cost and the decoding complexity affects the optimal information transmission. We find that the sub-threshold stimulation regime, although attaining the smallest capacity, allows for the most efficient balance between the information transmission and the metabolic cost. Furthermore, we determine post-synaptic firing rate histograms that are optimal from the information-theoretic point of view, which enables the comparison of our results with experimental data.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• akční potenciály fyziologie   MeSH
• energetický metabolismus fyziologie   MeSH
• gating iontového kanálu fyziologie   MeSH
• iontové kanály fyziologie   MeSH
• lidé MeSH
• membránové potenciály fyziologie   MeSH
• modely neurologické * MeSH
• nervový přenos fyziologie   MeSH
• neurony fyziologie   MeSH
• počítačová simulace MeSH
• ukládání a vyhledávání informací metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Recently, it has been suggested that certain neurons with Poissonian spiking statistics may communicate by discontinuously switching between two levels of firing intensity. Such a situation resembles in many ways the optimal information transmission protocol for the continuous-time Poisson channel known from information theory. In this contribution we employ the classical information-theoretic results to analyze the efficiency of such a transmission from different perspectives, emphasising the neurobiological viewpoint. We address both the ultimate limits, in terms of the information capacity under metabolic cost constraints, and the achievable bounds on performance at rates below capacity with fixed decoding error probability. In doing so we discuss optimal values of experimentally measurable quantities that can be compared with the actual neuronal recordings in a future effort.

• MeSH
• modely neurologické * MeSH
• nervový přenos fyziologie   MeSH
• neurony fyziologie   MeSH
• pravděpodobnost MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Recent studies on the theoretical performance of latency and rate code in single neurons have revealed that the ultimate accuracy is affected in a nontrivial way by aspects such as the level of spontaneous activity of presynaptic neurons, amount of neuronal noise or the duration of the time window used to determine the firing rate. This study explores how the optimal decoding performance and the corresponding conditions change when the energy expenditure of a neuron in order to spike and maintain the resting membrane potential is accounted for. It is shown that a nonzero amount of spontaneous activity remains essential for both the latency and the rate coding. Moreover, the optimal level of spontaneous activity does not change so much with respect to the intensity of the applied stimulus. Furthermore, the efficiency of the temporal and the rate code converge to an identical finite value if the neuronal activity is observed for an unlimited period of time.

• MeSH
• časové faktory MeSH
• energetický metabolismus * MeSH
• lidé MeSH
• membránové potenciály MeSH
• modely neurologické * MeSH
• nervová síť cytologie   fyziologie   MeSH
• neuronové sítě * MeSH
• neurony fyziologie   MeSH
• počítačová simulace MeSH
• výpočetní biologie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Rhomboid intramembrane proteases regulate pathophysiological processes, but their targeting in a disease context has never been achieved. We decoded the atypical substrate specificity of malaria rhomboid PfROM4, but found, unexpectedly, that it results from "steric exclusion": PfROM4 and canonical rhomboid proteases cannot cleave each other's substrates due to reciprocal juxtamembrane steric clashes. Instead, we engineered an optimal sequence that enhanced proteolysis >10-fold, and solved high-resolution structures to discover that boronates enhance inhibition >100-fold. A peptide boronate modeled on our "super-substrate" carrying one "steric-excluding" residue inhibited PfROM4 but not human rhomboid proteolysis. We further screened a library to discover an orthogonal alpha-ketoamide that potently inhibited PfROM4 but not human rhomboid proteolysis. Despite the membrane-immersed target and rapid invasion, ultrastructural analysis revealed that single-dosing blood-stage malaria cultures blocked host-cell invasion and cleared parasitemia. These observations establish a strategy for designing parasite-selective rhomboid inhibitors and expose a druggable dependence on rhomboid proteolysis in non-motile parasites.

• MeSH
• amidy chemická syntéza   chemie   farmakologie   MeSH
• antimalarika chemická syntéza   chemie   farmakologie   MeSH
• HEK293 buňky MeSH
• inhibitory proteas chemická syntéza   chemie   farmakologie   MeSH
• kyseliny boronové chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• malárie krev   farmakoterapie   metabolismus   MeSH
• molekulární struktura MeSH
• parazitické testy citlivosti MeSH
• peptidy chemická syntéza   chemie   farmakologie   MeSH
• Plasmodium falciparum účinky léků   metabolismus   MeSH
• proteasy krev   metabolismus   MeSH
• proteolýza účinky léků   MeSH
• protozoální proteiny antagonisté a inhibitory   krev   metabolismus   MeSH
• racionální návrh léčiv * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Cognitive impairment is a dramatically increasing problem affecting many individuals as well as the health system. As we have no causal treatment for the loss of memory, symptomatic treatment is needed. Influencing the ACh system is a generally accepted approach, although other therapeutic treatments are in various stages of development. The multiple target drug approach using hybrid compounds may be another optimized move forward for the treatment of cognitive disorders. - Since the complex neuronal regulation is slowly being decoded, there is hope that ways will be found to stop neuronal loss and to generate new synapses.

• MeSH
• amyloidní beta-protein škodlivé účinky   MeSH
• cholinesterasové inhibitory terapeutické užití   MeSH
• farmakoterapie MeSH
• fixní kombinace léků MeSH
• kognitivní poruchy dějiny   etiologie   farmakoterapie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• proteiny tau škodlivé účinky   MeSH
• receptory histaminu H3 terapeutické užití   MeSH
• receptory N-methyl-D-aspartátu antagonisté a inhibitory   terapeutické užití   MeSH
• Check Tag
• lidé MeSH