Multitasking in the olfactory system: context-dependent responses to odors reveal dual GABA-regulated coding mechanisms in single olfactory projection neurons.

Studies of olfaction have focused mainly on neural processing of information about the chemistry of odors, but olfactory stimuli have other properties that also affect central responses and thus influence behavior. In moths, continuous and intermittent stimulation with the same odor evokes two distinct flight behaviors, but the neural basis of this differential response is unknown. Here we show that certain projection neurons (PNs) in the primary olfactory center in the brain give context-dependent responses to a specific odor blend, and these responses are shaped in several ways by a bicuculline-sensitive GABA receptor. Pharmacological dissection of PN responses reveals that bicuculline blocks GABAA-type receptors/chloride channels in PNs, and that these receptors play a critical role in shaping the responses of these glomerular output neurons. The firing patterns of PNs are not odor-specific but are strongly modulated by the temporal pattern of the odor stimulus. Brief repetitive odor pulses evoke fast inhibitory potentials, followed by discrete bursts of action potentials that are phase-locked to the pulses. In contrast, the response to a single prolonged stimulus with the same odor is a series of slow oscillations underlying irregular firing. Bicuculline disrupts the timing of both types of responses, suggesting that GABAA-like receptors underlie both coding mechanisms. These results suggest that glomerular output neurons could use more than one coding scheme to represent a single olfactory stimulus. Moreover, these context-dependent odor responses encode information about both the chemical composition and the temporal pattern of the odor signal. Together with behavioral evidence, these findings suggest that context-dependent odor responses evoke different perceptions in the brain that provide the animal with important information about the spatiotemporal variations that occur in natural odor plumes.

GABAergic mechanisms that shape the temporal response to odors in moth olfactory projection neurons.

Mitral/tufted cells in the olfactory bulb and projection neurons (PNs) in the insect antennal lobe are involved in complex synaptic interactions with inhibitory interneurons to help shape their odor-evoked responses. In the moth Manduca sexta, both gamma-aminobutyric acid (GABA) and the GABAA receptor agonist muscimol hyperpolarize and lower input resistance in many PNs, often blocking ongoing spike traffic. The GABA response mimics a short-latency, chloride-mediated inhibitory postsynaptic potential (IPSP) evoked in PNs by electrical or odor stimulation of afferent inputs, and the classical GABAA receptor antagonist bicuculline methiodide (BMI) quickly and reversibly blocks this IPSP. Focal injection of BMI (100 microM) immediately preceding a GABA pulse blocks the hyperpolarization evoked by GABA, but a similar injection of BMI preceding an acetylcholine (ACh) pulse fails to block the depolarization evoked by ACh. Moreover, the temporal pattern of odor-evoked activity in moth PNs is also strongly and reversibly altered by BMI. Importantly, the temporal pattern of the response depends on the temporal characteristics of the stimulus: continuous stimulation evokes more complex, rhythmic responses, whereas a pulsatile stimulus can be copied with a discrete burst of spikes for each pulse. Collectively our results indicate that PNs in the moth antennal lobe possess GABA receptors that share certain characteristics in common with vertebrate GABAA receptors. These receptors are largely responsible for helping PNs integrate information about both the molecular features and the timing of olfactory input to the brain.

Local interneurons and information processing in the olfactory glomeruli of the moth Manduca sexta.

Intracellular recordings were made from the major neurites of local interneurons in the moth antennal lobe. Antennal nerve stimulation evoked 3 patterns of postsynaptic activity: (i) a short-latency compound excitatory postsynaptic potential that, based on electrical stimulation of the antennal nerve and stimulation of the antenna with odors, represents a monosynaptic input from olfactory afferent axons (71 out of 86 neurons), (ii) a delayed activation of firing in response to both electrical- and odor-driven input (11 neurons), and (iii) a delayed membrane hyperpolarization in response to antennal nerve input (4 neurons). Simultaneous intracellular recordings from a local interneuron with short-latency responses and a projection (output) neuron revealed unidirectional synaptic interactions between these two cell types. In 20% of the 30 pairs studied, spontaneous and current-induced spiking activity in a local interneuron correlated with hyperpolarization and suppression of firing in a projection neuron. No evidence for recurrent or feedback inhibition of projection neurons was found. Furthermore, suppression of firing in an inhibitory local interneuron led to an increase in firing in the normally quiescent projection neuron, suggesting that a disinhibitory pathway may mediate excitation in projection neurons. This is the first direct evidence of an inhibitory role for local interneurons in olfactory information processing in insects. Through different types of multisynaptic interactions with projection neurons, local interneurons help to generate and shape the output from olfactory glomeruli in the antennal lobe.

The roles of local interneurons in the processing of olfactory information in the antennal lobes of the moth Manduca sexta.

The antennal lobe (AL) of the sphinx month Manduca sexta is characterized by a typically glomerular neuropil and two principal classes to neurons local interneurons and projection neurons. The somata of these neurons reside in defined neural cell-body groups in the AL, and the neurons exhibit characteristic patterns of innervation of the glomeruli. Evidence gathered to date indicates that individual antennal olfactory receptor-cell axons project to single glomeruli in the ipsilateral AL and make excitatory, apparently cholinergic synapses with neurites of AL neurons (usually local neurons) innervating the target glomeruli. Much has been learned about the physiology of the projection neurons, but only recently have the physiological properties and functions of the local interneurons been examined systematically through the use of intracellular recording and staining methods. Immunocytochemical studies have shown that most of the local interneurons contain GABA as well as one or more putative neuropeptides. Physiological, pharmacological, and biochemical experiments support the view that GABAergic local interneurons are responsible for inhibitory synaptic inputs to projection neurons that predominate in shaping the activity of projection neurons conveying synaptically processed olfactory information to higher-order centers in the protocerebrum.