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, 8 (12), e1000567

A Novel Neural Substrate for the Transformation of Olfactory Inputs Into Motor Output

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A Novel Neural Substrate for the Transformation of Olfactory Inputs Into Motor Output

Dominique Derjean et al. PLoS Biol.

Abstract

It is widely recognized that animals respond to odors by generating or modulating specific motor behaviors. These reactions are important for daily activities, reproduction, and survival. In the sea lamprey, mating occurs after ovulated females are attracted to spawning sites by male sex pheromones. The ubiquity and reliability of olfactory-motor behavioral responses in vertebrates suggest tight coupling between the olfactory system and brain areas controlling movements. However, the circuitry and the underlying cellular neural mechanisms remain largely unknown. Using lamprey brain preparations, and electrophysiology, calcium imaging, and tract tracing experiments, we describe the neural substrate responsible for transforming an olfactory input into a locomotor output. We found that olfactory stimulation with naturally occurring odors and pheromones induced large excitatory responses in reticulospinal cells, the command neurons for locomotion. We have also identified the anatomy and physiology of this circuit. The olfactory input was relayed in the medial part of the olfactory bulb, in the posterior tuberculum, in the mesencephalic locomotor region, to finally reach reticulospinal cells in the hindbrain. Activation of this olfactory-motor pathway generated rhythmic ventral root discharges and swimming movements. Our study bridges the gap between behavior and cellular neural mechanisms in vertebrates, identifying a specific subsystem within the CNS, dedicated to producing motor responses to olfactory inputs.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Olfactory epithelium stimulation activates RS cells.
(A) Illustration of the experimental procedure in an isolated olfactory epithelium-brain-spinal cord preparation. (B) Responses of RS cell to the application of L-arginine over the olfactory epithelium (Arg, 1 mM). (C) Response to bile acid–taurocholic acid (TCA, 1 µM). (D–E) Responses to male-secreted pheromones, 3-keto-petromyzonol sulfate (3KPZS, 10 µM), and 3-keto allocholic acid (3KACA, 10 µM), respectively. Arrows represent the onset of odor ejection. (B–E) are from different preparations.
Figure 2
Figure 2. Olfactory nerve stimulation activates RS cells.
(A) Responses of RS cells following electrical stimulation of the ON with 5 or 15 µA (top versus bottom traces); single shocks or trains of stimulation (left versus right traces). Each trace is a mean of eight individual responses. (B) Calcium fluorescence imaging illustrates the ΔF/F response of identified RS cells to ON stimulation (20 µA –10 Hz). (a, c) ipsilateral. (b, d) contralateral. White scale bar in the photomicrograph represents 100 µm. (C) RS responses to ON electrical stimulation are reduced by glutamate antagonists perfused through the bath (50 µA stimulation, upper traces) (D) or injected onto the OB (50 µA stimulation, bottom traces).
Figure 3
Figure 3. Glutamate injection into the OB induces fictive locomotion.
(A) Top trace: Intracellular recording of a RS cell. Note the large excitation induced by the injection of 3 mM glutamate in the ipsilateral OB. Bottom traces: Ventral root (VR) discharges on both sides. (B) Detail from the boxed area in (B) shows fictive locomotion characterized by alternating ipsilateral and contralateral ventral root activity (iVR and cVR, respectively). Note that the RS cell shows rhythmic oscillations in tune with the fictive locomotor pattern.
Figure 4
Figure 4. Olfactory-locomotor information transits through the medial region of the OB.
(A–D) Responses in a single ipsilateral RS neuron to 30 µA stimulation of the ON and OB. The schematic (inset) indicates the location of stimulating electrodes. Note that a synaptic response was elicited only following stimulation of the ON or the medial part of the OB. (E) Mean amplitude of 4 RS cells responses to 30 µA ON stimulation before (grey bar) and after local injection of AP5 and CNQX mixture in the central-medial OB (red bar) and lateral OB (green bar). * p<0.05.
Figure 5
Figure 5. The medial region of the OB projects to the PT.
(A) Schematic dorsal view of the forebrain summarizing the efferent OB projections in the lamprey. Projections from OB regions other than the medial region are shown in green. (B) Anterograde labeling from the medial OB (red) shows fibers terminating in the PT (see picture to the right). (C, D) Retrograde labeling from the PT shows neuronal cell bodies in only one medial glomerulus in the OB (see picture to the right). (E, F) Retrograde labeling from the lateral pallium shows neurons associated with almost all glomeruli, except the medial. White scale bars in pictures represent 100 µm.
Figure 6
Figure 6. Stimulation of the PT activates RS neurons and locomotion.
(A) PT stimulation induces RS responses. Raising the stimulation intensity from 2 to 5 µA increases the amplitude of the evoked synaptic responses (left two traces), while a short stimulation train (10 µA –5 Hz) elicited a long-lasting afterdischarge in the same RS cell (right trace). (B) Illustration of the semi-intact preparation. (C) Glutamate (3 mM) injected into the PT elicited swimming and bursts of activity on EMG recordings. iEMG, ipsilateral; cEMG, contralateral. (D) Enlargement of the boxed area in (C) shows left and right muscle contractions.
Figure 7
Figure 7. Olfactory inputs are relayed via the PT and MLR.
(A) Schematic illustration showing the experimental procedure where glutamate receptor antagonists were injected in different sites indicated by the arrows. (B) RS cell responses to ON stimulation are strongly decreased by the injection in the PT. (C) Injection in the MLR has a similar effect. (D) An injection in the DLR does not block the synaptic responses. (B, C, D) are from different preparations.
Figure 8
Figure 8. Schematic representation of the olfactory-locomotor circuitry in lampreys.
Stimulation of the olfactory sensory neurons in the periphery activates neurons in the OB. There are two distinct projections from the OB, one from the lateral and another from the medial part. The lateral part projects to forebrain structures including the lateral pallium, the striatum with some fibers reaching down to habenula (grey arrows). The medial part is the relevant part for generating locomotor behavior. There is a direct projection from the medial part of the OB to the PT. From the PT, there is a projection to the MLR, known to play a crucial role in controlling locomotion in all vertebrate species. MLR neurons project to brainstem reticulospinal neurons, acting as command cells for locomotion. RS cells, in turn, project directly to spinal cord neurons that generate the basic muscle synergies responsible for propulsion during locomotion.

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