Decorrelation of Odor Representations via Spike Timing-Dependent Plasticity

The non-topographical representation of odor quality space differentiates early olfactory representations from those in other sensory systems. Decorrelation among olfactory representations with respect to physical odorant similarities has been proposed to rely upon local feed-forward inhibitory circuits in the glomerular layer that decorrelate odor representations with respect to the intrinsically high-dimensional space of ligand–receptor potency relationships. A second stage of decorrelation is likely to be mediated by the circuitry of the olfactory bulb external plexiform layer. Computations in this layer, or in the analogous interneuronal network of the insect antennal lobe, are dependent on fast network oscillations that regulate the timing of mitral cell and projection neuron (MC/PN) action potentials; this suggests a largely spike timing-dependent metric for representing odor information, here proposed to be a precedence code. We first illustrate how the rate coding metric of the glomerular layer can be transformed into a spike precedence code in MC/PNs. We then show how this mechanism of representation, combined with spike timing-dependent plasticity at MC/PN output synapses, can progressively decorrelate high-dimensional, non-topographical odor representations in third-layer olfactory neurons. Reducing MC/PN oscillations abolishes the spike precedence code and blocks this progressive decorrelation, demonstrating the learning network's selectivity for these sparsely synchronized MC/PN spikes even in the presence of temporally disorganized background activity. Finally, we apply this model to odor representations derived from calcium imaging in the honeybee antennal lobe, and show how odor learning progressively decorrelates odor representations, and how the abolition of PN oscillations impairs odor discrimination

Internal Cholinergic Regulation of Learning and Recall in a Model of Olfactory Processing

In the olfactory system, cholinergic modulation has been associated with contrast modulation and changes in receptive fields in the olfactory bulb, as well the learning of odor associations in olfactory cortex. Computational modeling and behavioral studies suggest that cholinergic modulation could improve sensory processing and learning while preventing pro-active interference when task demands are high. However, how sensory inputs and/or learning regulate incoming modulation has not yet been elucidated. We here use a computational model of the olfactory bulb, piriform cortex (PC) and horizontal limb of the diagonal band of Broca (HDB) to explore how olfactory learning could regulate cholinergic inputs to the system in a closed feedback loop. In our model, the novelty of an odor is reflected in firing rates and sparseness of cortical neurons in response to that odor and these firing rates can directly regulate learning in the system by modifying cholinergic inputs to the system. In the model, cholinergic neurons reduce their firing in response to familiar odors—reducing plasticity in the PC, but increase their firing in response to novel odor—increasing PC plasticity. Recordings from HDB neurons in awake behaving rats reflect predictions from the model by showing that a subset of neurons decrease their firing as an odor becomes familiar

Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity

Background Ebolaviruses cause a severe and often fatal haemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently, the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission. Results To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naïve animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage. Conclusions Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV

Cholinergic agonist carbachol enables associative long-term potentiation in piriform cortex slices

Michael E. Hasselmo. Cholinergic agonist carbachol enables asso- standard experimental protocol for induction of LTP in brain ciative long-term potentiation in piriform cortex slices. J. Neuro- slice preparations of the hippocampus (Madison et al. 1991). physiol. 80: 2467–2474, 1998. Pyramidal cells in piriform (olfac- More recently, Kanter and Haberly (1993) have shown that tory) cortex receive afferent input from the olfactory bulb as well another form of LTP, associative LTP, can be induced beas intrinsic association input from piriform cortex and other cortical areas. These two functionally distinct inputs terminate on adjacent tween the afferent and the association fiber layer when the apical dendritic segments of the pyramidal cells located in layer fast, chloride-mediated inhibition is blocked. In the associa-Ia and layer Ib of piriform cortex. Studies with bath-applied cholin- tive LTP paradigm, a weak, (nonpotentiating) stimulus to ergic agonists have shown suppression of the fast component of the one set of fibers can produce potentiation if paired with a inhibitory postsynaptic potentials (IPSPs) evoked by stimulation strong (potentiating) stimulus to the second set of fibers of the association fibers. It was previously demonstrated that an associative form of LTP can be induced by coactivation of the two fiber systems after blockade of the fast, g-aminobutyric acid-A– mediated IPSP. In this report, we demonstrate that an associative form of long-term potentiation can be induced by coactivation of afferent and intrinsic fibers in the presence of the cholinergic ago-(Barrinuevo and Brown 1983; Levy and Steward 1979). In piriform cortex, this form of associative LTP between affer-ent input (in layer Ia) and association fibers (in layer Ib) could only be obtained when chloride-mediated inhibition was blocked (Kanter and Haberly 1993). nist carbachol. Experiments in our laboratory have shown a strong, selec

Size of CA1-evoked synaptic potentials is related to theta rhythm phase in rat hippocampus

Size of CA1-evoked synaptic potentials is related to theta rhythm phase in rat hippocampus. J. Neurophysiol. 83: 2138–2144, 2000. Cholinergic and GABAergic neurons projecting to the hippocampus fire with specific phase relations to theta rhythm oscillations in the electroencephalogram (EEG). To determine if this phasic input has an impact on synaptic transmission within the hippocampus, we recorded evoked population excitatory postsynaptic potential (EPSPs) during different phases of theta rhythm by using techniques similar to those described in Rudell and Fox. Synaptic potentials elicited by stimulation of region CA3 of the contralateral hippocampus were recorded in region CA1 and CA3. In these experiments, the initial slope of evoked potentials showed a change in magnitude during different phases of the theta rhythm recorded in the dentate fissure, with individual trials showing an average of 9.5 % change in slope of potentials, and the average across all experiments showing a change of 7.8%. Evoked potentials were maximal 18 ° after the positive peak of the dentate fissure theta EEG. These potentials were also smaller by 18.2 % during theta as opposed to non-theta states. Phasic changes in modulation of synaptic transmission could contribute to phase precession of hippocampal place cells and could enhance storage of new sequences of activity as demonstrated by computational models