Lecture 4: Chemical Senses

Olfaction as a Multidimensional Coding Space

  • Dimensionality Comparison across Sensory Modalities:

    • Sound: Characterized by limited dimensions such as intensity and frequency.

    • Light: Characterized by location, intensity, and wavelength (perceived as color).

    • Odour: Unlike sound or light, olfaction operates in a highly complex, multidimensional coding space due to the vast variety of chemical structures that can act as odorants.

  • Coding Strategies in the Nervous System:

    • Labelled Line Code:

      • Specific to evolutionarily important stimuli (e.g., sex pheromones in moths).

      • A single receptor type links directly to a specific neural channel and a dedicated output (e.g., a "sweet" receptor leads directly to a "sweet" perception).

      • This is less common for general odors because it would require one specific neuron and channel for every possible stimulus.

    • Combinatorial (Pattern) Code:

      • Multiple neurons respond to multiple stimuli.

      • A single odorant activates a specific combination of receptors.

      • The CNS employs a pattern decoder to identify the stimulus based on the ensemble of activated neurons. This allows for an exponential increase in the number of identifiable odors compared to the number of receptor types.

Comparative Biology of Chemical Senses

  • Species Studied: Key insights in neural circuits are derived from comparing mammals (such as mice and humans) and insects (specifically Drosophila).

  • Importance of Evolution: Comparing divergent species helps identify conserved features and fundamental principles that are essential for sensory processing.

Olfactory Sensory Transduction and Neuron Specificity

  • Sensory Transduction Mechanisms:

    • Mammals: Utilize second messengers to amplify sensory signals.

    • Insects: In a notable contrast, insect olfactory receptors function as ion channels.

  • Receptor Profiles:

    • Each olfactory receptor responds to a unique profile of odorants (Hallem and Carlson, 2004).

    • Experiments involving Drosophila olfactory receptor neurons (ORNs) where native receptors were replaced with experimenter-selected receptors confirm that the response profile is determined by the specific receptor expressed.

  • Single Receptor Expression:

    • As olfactory sensory neurons mature, they narrow their expression down to a single type of olfactory receptor per neuron.

    • This has been confirmed through single-cell whole transcriptome sequencing (Hanchate et al., 2015).

Neural Architecture: The Glomerulus and First Relay Synapse

  • Convergence and the Glomerulus:

    • Definition: "Glomerulus" is Latin for "little ball of thread."

    • Organization: All olfactory sensory neurons expressing the same receptor type converge onto the same glomerulus (Mombaerts et al., 1996 for mice; Fishilevich and Vosshall, 2005 for Drosophila).

    • The glomerulus is located in the olfactory bulb (mammals) or the antennal lobe (insects).

  • Second-Order Neurons:

    • Sensory neurons transfer information to second-order neurons at the glomeruli.

    • Mammals: Olfactory sensory neurons (OSNs) connect to Mitral cells and Tufted cells. Local processing involves Granule cells and Periglomerular cells.

    • Insects: Olfactory receptor neurons (ORNs) connect to Projection neurons (PNs). Local processing involves Local neurons (LNs).

    • Role of Specificity: Receptor-specific matching ensuring that the chemical specificity encoded at the periphery is preserved as it is carried deeper into the brain.

Computational Transformations at the First Relay Synapse

  • Transformation Objectives: The first relay synapse (between sensory neurons and second-order neurons) does not just pass signals; it transforms the code.

  • Temporal Filtering (Synaptic Adaptation):

    • Synaptic adaptation emphasizes the start (onset) of the odour stimulus (Bhandawat et al., 2007).

  • Noise Reduction and Sensitivity:

    • Multiple sensory neurons converge onto fewer second-order neurons.

    • This reduces neural noise and strengthens responses to weak stimuli.

  • Lateral Inter-glomerular Cross-talk:

    1. Gain Control: Lateral inhibition allows the system to remain sensitive to both very weak and very strong odors, preventing saturation (Olsen et al., 2010).

    2. De-correlation: Inhibitory cross-talk makes the responses of the neuronal population to different odors as distinct (different) as possible, enhancing discrimination (Banerjee et al., 2015).

Higher Brain Pathways and Behaviour

  • Anatomical Pathways:

    • Insects: Projection neurons (PNs) send information to the Mushroom Body (Kenyon cells) and the Lateral Horn.

    • Humans/Mammals: Information travels to the Piriform Cortex, Amygdala, Entorhinal Cortex, Hippocampus, Thalamus, Insula, and Orbitofrontal Cortex (OFC).

  • Functional Specialization:

    • Learned Behaviour: Processes occur in the Piriform Cortex (mammals) and the Mushroom Body (insects).

    • Innate Behaviour: Processes occur in the Amygdala (mammals) and the Lateral Horn (insects).

  • Case Study: Cortical Amygdala:

    • Required for innate responses, such as mice avoiding the smell of fox odour (TMT).

    • Silencing the cortical amygdala abolishes this avoidance behaviour (Root et al., 2014).

  • Coding Differences:

    • Innate Circuitry: Utilizes dense codes and stereotyped connectivity to categorize specific preferred stimuli.

    • Learning Circuitry: Utilizes sparse codes and random connectivity to discriminate between arbitrary odors.

Olfactory Search Strategies

  • Biased Random Walk:

    • Observed in Bacteria (E. coli) and C. elegans.

    • Rule: If environmental conditions are improving (e.g., increasing nutrient concentration), the organism performs more "runs" (straight swimming) and fewer "tumbles" (turning).

  • Complex Strategies in Insects and Mammals:

    1. Upwind Flight: Flying against the wind when an attractive odour is detected.

    2. Turbulence Management: If the odour is lost, the organism waits briefly before turning, a strategy for navigating turbulent odour plumes.

    3. Multimodal Integration: Using other sensory cues (visual, tactile) once the source is near.

  • Active Sensing:

    • Head Movements: Moving the head samples a larger space and generates rapid changes in detected odour concentration.

    • Sniff Cycles: Coordinating sniffing with head movement to optimize detection.

    • Human Application: Humans can also perform olfactory search behaviours (Porter et al., 2007).

Gustatory (Taste) Transduction and Circuits

  • Taste Transduction Mechanisms:

    • Sweet, Bitter, and Umami: Use Metabotropic GPCRs (G protein-coupled receptors). Signaling involves PLCβ2PLC\beta 2, IP3R3IP_3R3, and the opening of TrpM5TrpM5 channels, leading to the release of ATP via Panx1Panx1.

    • Sour: Uses ionotropic proton-sensitive channels (H+H^+).

    • Salt: Uses sodium channels (ENaCENaC).

    • Signal amplification is a key feature in these pathways.

  • Human Taste Anatomy:

    • Sensory input from taste buds (Cranial nerves VII, IX, and X) converges in the Solitary Nucleus of the brainstem.

    • Information travels to the Ventral Posterior Medial (VPM) nucleus of the Thalamus and then to the Insula (Primary Gustatory Cortex) and Parietal Cortex.

    • Pathways also connect to the Hypothalamus and Amygdala.

  • Lateral Inhibition in Taste:

    • In Drosophila, bitter stimuli can trigger GABAergic interneurons that release GABA onto the presynaptic terminals of sweet-sensing neurons, inhibiting sweet responses so the fly avoids eating a mixture of sweet and bitter compounds (Chu et al., 2014).

  • Cortical Representation:

    • The mouse insula contains "hot spots" specific to different tastes.

    • Optogenetic activation of "sweet" areas induces approach, while activating "bitter" areas induces avoidance (Peng et al., 2015).

Formative Questions and Discussion

  • Question 1: If local inhibitory neurons in the mouse olfactory bulb are blocked, what is the predicted outcome?

    • Answer: Mice would be less able to behaviorally discriminate between different odors (due to loss of de-correlation) and less able to handle high concentrations (due to loss of gain control).

  • Question 2: Which mechanism helps animals find an odour source via a biased random walk?

    • Answer: Mechanisms that regulate the frequency of "tumbles" or turns based on whether the detected concentration is increasing or decreasing.