The origins of electrical discharge patterns in the main olfactory bulb of the rat

Landmark discoveries made in the olfactory bulb have formed the basis of much of our understanding of other brain regions. In fact, it was in the olfactory bulb that the first example of a dendrodentritic synapse in the mammalian central nervous system was found. The olfactory bulb is rich in a diverse selection of neurotransmitters, and with the bonus that the bulb is relatively easy to access, it provides an excellent model in which to study neural networks.The aim of this PhD project was to study the neural pathway that is thought to connect the olfactory bulb to the supraoptic nucleus of the hypothalamus. To understand the input to the supraoptic nucleus from the olfactory system we sought to determine the discharge frequency and firing pattern of the output neurones, mitral cells. The electrical activity of single neurones was recorded extracellularly from the olfactory bulb of anaesthetised rats. Mitral cells were identified electrophysiologically by antidromic activation following stimulation of the lateral olfactory tract and observation of bulbar field potentials. It became apparent that the mitral cells consistently showed a spontaneous patterned discharge that has not been previously reported and we have described this pattern in terms of three separate levels of bursting behaviour.What we have termed the 'gross' phasic pattern was displayed by all mitral cells and consisted of a characteristic slow, cyclic firing pattern with peaks of activity occurring with a constant periodicity, burst lengths lasted for approximately two minutes with equal periods of quiescence separating the bursts. Some mitral cells (53 %) show distinct silent periods between bursts of high activity others (47 %) simply show a reduced rate of activity between bursts. Auto -correlation plots show that within this overall phasic pattern is a respiratory driven bursting activity, the activity of mitral cells increases during the inspiratory phase as air is drawn over the olfactory receptors in the nasal mucosa. Plotting the instantaneous frequency of mitral cell activity reveals the third bursting pattern, exhibited by 57% of mitral cells recorded. This shows that during each long burst of activity the mitral cell fires at two distinct frequencies, the lower frequency is in the range 0 -50Hz and the high frequency firing is in the range 100- 250Hz. In 84% of the bursts that showed two distinct firing frequencies there was a delay in the onset of the higher frequency mode, at the start of each peak of activity. Mitral cells have been shown to be capable of initiating and propagating action potentials from their distal dendrites, as well as from the conventional initiation site at the soma -axon hillock region. It is proposed in this thesis that the high frequency firing mode described might be generated in the mitral cell dendrites.The mitral cell is involved in complex interactions with both neighbouring mitral cells and granule cells that provide for lateral and reciprocal inhibition respectively. Granule cells are the most numerous of the various types of interneurone in the bulb and their firing pattern was found to be non-phasic and at only one frequency mode. Following stimulation of the lateral olfactory tract mitral cells exhibited a period of inhibition following the stimulus pulse. This is consistent with the general consensus that upon activation, mitral cells activate granule cells, which in turn feedback to inhibit the mitral cells (reciprocal inhibition). Extracellular recordings of mitral cell activity were also made in a slice preparation of the olfactory bulb. It was discovered that in vitro the mitral cells did not discharge in a slow, phasic pattern and the high frequency firing seen in vivo was not evident. During the slice preparation many of the long lateral dendrites of the mitral cells are unavoidably removed and this may disturb the local interactions and thereby alter the discharge pattern.Once the discharge pattern of olfactory neurones was determined these parameters were then used as a basis for the stimulation of the lateral olfactory tract and the effect on supraoptic neurone activity determined by studying the distribution of Fos -positive cells. Two stimulation protocols were used both were strong stimuli applied unilaterally, in different formats. The first was a short burst at a high frequency to mimic an acute, strong output from the olfactory bulb and the second Abstract x was a prolonged stimulation used to disrupt the output discharge pattern. The literature suggests that the connection between the olfactory bulb and the supraoptic nucleus is unilateral, monosynaptic and terminates in the ventro -lateral dendritic region of the supraoptic nucleus. Following prolonged stimulation of the lateral olfactory tract there was a significant increase (p <0.01) in Fos expression in the supraoptic nucleus on both the ipsilateral and contralateral sides which suggests that the pathway between the olfactory bulb and the supraoptic nucleus may be more complex than initially thought. Areas of the brain known to receive strong olfactory input, such as the piriform cortex, showed a unilateral increase in Fos expression following the brief pulse of stimulation.Administration of morphine during parturition interrupts the progress of parturition by inhibiting oxytocin release. The olfactory bulb is highly active at the time of parturition and shows dense expression of mu- and kappa opioid receptors, and so the possibility that morphine may impair oxytocin release in part by blocking the input from the olfactory bulb was considered. The effect of morphine and its antagonist, naloxone on the discharge pattern of mitral cells was studied in both the in vivo and in vitro preparations. In vivo morphine was seen to have a subtle effect in that it inhibited the high frequency firing but did not significantly alter the overall firing rate or periodicity of bursts, this effect was irreversible. However, in vitro morphine fully inhibited mitral cell activity which returned to pre -morphine rates following the administration of naloxone. The discrepancy between the two sets of data may be a dose issue. In vivo the drugs were administered via an intravenous route which may have led to a reduced concentration of the drug evoking a response from the mitral cells compared to the concentration of the drug that the mitral cells in vitro were exposed to. It may also be due to the reduced local circuitary of the mitral cell in the in vitro preparation, causing the mitral cell to become more susceptible to the effects of morphine

What you didn't see:Prevention and generation in continuous time causal induction

How do people use temporal information to make causal judg-ments? A number of studies have investigated the role of timein inferring generative causal structure, while few have exam-ined prevention. Here, we focus on a challenging task in whichparticipants learn the structure of several causal “devices” bywatching the devices’ patterns of activation over time. Eachdevice potentially includes both generative (producing an acti-vation of its effect) and preventative (blocking any effect acti-vations within a short time window) causal relationships. Weexamine judgment patterns through the lens of a normativemodel which incorporates actual causation with considerationsof prevention. We contrast this with a more computationallytractable feature-based approximation. Participants’ perfor-mance was substantially above chance in all conditions. Themajority of participants’ causal judgments were best fit by thefeature-based approximation based on delay and count heuris-tic cues

Inferring epistemic intention in simulated physical microworlds

We explore whether people can recognise the epistemic goal of active learners. In a novel online experiment, 110 adults watched screen recordings of other adults (``players'') manipulating objects in a 2D simulated physical microworld. Players had the goal of either identifying the magnet-like force connecting two of the objects, or their relative masses. Observers were asked to identify the learning goal of the player. By drawing from a previously collected dataset of active physical learning interactions and an ideal observer analysis, we manipulated how informative the players' actions are about the target property, and observers' level of access to the players' micro-control actions. We found observers were better at identifying the goals of successful players and of players trying to identify force, while the micro-dynamic evidence improved accuracy on identifying the mass goal. We use mixed methods to explore what cues observers used to make these judgments

Evidence from the future

The outcome of any scientific experiment or intervention will naturally unfold over time. How then should individuals make causal inferences from measurements over time? Across three experiments, we had participants observe experimental and control groups over several days post-treatment in a fictional biological research setting. We identify competing perspectives in the literature: Contingency-driven accounts predict no effect of outcome timing while the contiguity principle suggests people will view a treatment as more harmful to the extent that bad treatment outcomes occur earlier rather than later. In contrast, inference to the functional form of a treatment effect can license extrapolation beyond the measurements and lead to different causal inferences. We find participants’ causal strength and direction judgments in temporal settings vary with minimal manipulations of instruction framing. When it is implied that the observations are made over a pre-planned number of days, causal judgments depend strongly on contiguity. When it is implied that the observation may be ongoing, participants extrapolate current trends into the future and adapt their causal judgments accordingly. When data are revealed sequentially, participants rely on extrapolation regardless of instruction framing. Our results demonstrate human flexibility in interpreting temporal evidence for causal reasoning and emphasize human tendency to generalize from evidence in ways that are acutely sensitive to task framing

Learning preventative and generative causal structures from point events in continuous time

Many previous accounts of causal structure induction have focused on atemporalcontingency data while fewer have described learning on the basis of observations of events unfolding over time. How do people use temporal information to infer causal structures? Here we develop a computational-level framework and propose several algorithmic-level approximations to explain how people impute causal structures from continuous-time event sequences. We compare both normative and process accounts to participant behavior across two experiments. We consider structures combining both generative and preventative causal relationships in the presence of either regular or irregular background noise in the form of spontaneous activations. We find that 1) humans are robustly capable learners in this setting, successfully identifying a variety of ground truth structures but 2) diverging from our computational-level account in ways we can explain with a more tractable simulation and summary statistics approximation scheme. We thus argue that human structure induction from temporal information relies on comparisons between observed patterns and expectations established via mental simulation