GABAergic modulation of olfactomotor transmission in lampreys

Abstract

Odor-guided behaviors, including homing, predator avoidance, or food and mate searching, are ubiquitous in animals. It is only recently that the neural substrate underlying olfactomotor behaviors in vertebrates was uncovered in lampreys. It consists of a neural pathway extending from the medial part of the olfactory bulb (medOB) to locomotor control centers in the brainstem via a single relay in the caudal diencephalon. This hardwired olfactomotor pathway is present throughout life and may be responsible for the olfactory-induced motor behaviors seen at all life stages. We investigated modulatory mechanisms acting on this pathway by conducting anatomical (tract tracing and immunohistochemistry) and physiological (intracellular recordings and calcium imaging) experiments on lamprey brain preparations. We show that the GABAergic circuitry of the olfactory bulb (OB) acts as a gatekeeper of this hardwired sensorimotor pathway. We also demonstrate the presence of a novel olfactomotor pathway that originates in the non-medOB and consists of a projection to the lateral pallium (LPal) that, in turn, projects to the caudal diencephalon and to the mesencephalic locomotor region (MLR). Our results indicate that olfactory inputs can induce behavioral responses by activating brain locomotor centers via two distinct pathways that are strongly modulated by GABA in the OB. The existence of segregated olfactory subsystems in lampreys suggests that the organization of the olfactory system in functional clusters may be a common ancestral trait of vertebrates.

Gain control in the sensorimotor system

“…Olfactory cues also trigger strong behavioral responses in a variety of species, suggesting that this sensory modality is also subject to context-dependent gain control. Indeed, recent work identified inhibitory neurons in the lamprey olfactory bulb that can modulate hardwired feedback pathways, providing a potential explanation for how the same olfactory-cues can produce divergent sex-and life-stage-specific locomotor responses [22]. Together, these studies further support the idea that inhibition of incoming signals provides a conserved means across species and sensory modalities for ensuring that disruptive feedback does not aberrantly influence motor output.…”

Dopaminergic modulation of olfactory‐evoked motor output in sea lampreys (Petromyzon marinus L.)

“…Hence, electrophysiological experiments were carried out to characterize the physiological effects of DA on the medial olfactomotor pathway (Derjean et al, ). Projection neurons in the medOB send direct output to the PT and to the MLR, which relay the signal to RS cells to generate locomotor activity (Daghfous et al, ; Derjean et al, ). The recording of RS cells, which act as command cells for locomotion, can monitor this activity.…”

“…Streptavidin conjugated to Alexa Fluor 488 or 350 (diluted 1:200, S11223 or S11249, Thermo Fisher Scientific) was added to the secondary antibody solution to visualize biocytin. The primary olfactory afferents were stained with Griffonia simplicifolia isolectin B4 (GSIB4), which binds to galactosyl residues present on axons of olfactory sensory neurons, as previously done by others (Tobet, Chickering, & Sower, ) and us (Daghfous et al, ). This labeling was carried out after the immunofluorescence protocol by incubating the slides with GSIB4 conjugated to Alexa Fluor 488 (I21411, Life Technologies) diluted 1:100 in the appropriate rinsing solution (TBS‐m or PBS) for 60 min at room temperature.…”

“…Recent findings in our lab have revealed that olfactory projections from the rest of the OB (main OB: MOB) can also activate the PT, but via projections to the lateral pallium (Daghfous et al, ). The well‐characterized, locomotion‐controlling neural circuits that are part of an axis from the PT to the spinal cord can thus be activated by both a medial (medOB‐PT) and a lateral (MOB‐lateral pallium‐PT) olfactomotor pathways to generate locomotor responses to olfactory cues.…”

“…Odorant detection is carried out by olfactory sensory neurons that project to the medial part of the OB (medOB; Green et al, ). There, a unique population of projection neurons located inside a single glomerulus (medOB glomerulus) conveys the inputs to the posterior tuberculum (PT; Daghfous et al, ; Derjean et al, ; Green, Basilious, Dubuc, & Zielinski, ; Pérez‐Fernández, Stephenson‐Jones, Suryanarayana, Robertson, & Grillner, ). The PT then sends descending dopaminergic and glutamatergic inputs to the mesencephalic locomotor region (MLR; Ryczko et al, , , ), a structure known to play a crucial role in the control of locomotion in all vertebrate species tested so far.…”