Spiking and Membrane Properties of Rat Olfactory Bulb Dopamine Neurons

Abstract

The mammalian olfactory bulb (OB) has a vast population of dopamine (DA) neurons, whose function is to increase odor discrimination through mostly inhibitory synaptic mechanisms. However, it is not well understood whether there is more than one neuronal type of OB DA neuron, how these neurons respond to different stimuli, and the ionic mechanisms behind those responses. In this study, we used a transgenic rat line (hTH-GFP) to identify fluorescent OB DA neurons for recording via wholecell electrophysiology. These neurons were grouped based on their localization in the glomerular layer ("Top" vs. "Bottom") with these largest and smallest neurons grouped by neuronal area ("Large" vs. "Small," in µm 2 ). We found that some membrane properties could be distinguished based on a neuron's area, but not by its glomerular localization. All OB DA neurons produced a single action potential when receiving a sufficiently depolarizing stimulus, while some could also spike multiple times when receiving weaker stimuli, an activity that was more likely in Large than Small neurons. This single spiking activity is likely driven by the Na + current, which showed a sensitivity to inactivation by depolarization and a relatively long time constant for the removal of inactivation. These recordings showed that Small neurons were more sensitive to inactivation of Na + current at membrane potentials of −70 and −60 mV than Large neurons. The hyperpolarizationactivated H-current (identified by voltage sags) was more pronounced in Small than Large DA neurons across hyperpolarized membrane potentials. Lastly, to mimic a more physiological stimulus, these neurons received ramp stimuli of various durations and current amplitudes. When stimulated with weaker/shallow ramps, the neurons needed less current to begin and end firing and they produced more action potentials at a slower frequency. These spiking properties were further analyzed between the four groups of neurons, and these analyses support the difference in spiking induced with current step stimuli. Thus, there may be more than one type of OB DA neuron, and these neurons' activities may support a possible role of being high-pass filters in the OB by allowing the transmission of stronger odor signals while inhibiting weaker ones.

Illuminating and Sniffing Out the Neuromodulatory Roles of Dopamine in the Retina and Olfactory Bulb

“…We also found that, when these neurons were grouped based on their neuronal areas (in which we classified them as either "Large" or "Small" dopamine neurons), the Large dopamine neurons produced more action potentials in response to weak current stimuli, while the Small neurons only produced a more phasic/single spiking response to these stimuli (Korshunov et al, 2020). When stimulated with stronger current stimuli, the Large and Small neurons both produced the same phasic/single spiking response (Korshunov et al, 2020). This difference in responses was likely due to inactivation properties of the voltage-gated Na + (Na V ) channels.…”

“…For example, none of the neurons from which we recorded displayed spontaneous spiking, only showing synaptically driven potentiation; this indicates a potential functional difference in the background activity between rat and mouse OB dopamine neurons, suggesting a possible functional and species difference (Pignatelli et al, 2005;Puopolo et al, 2005;Korshunov et al, 2020). We also found that, when these neurons were grouped based on their neuronal areas (in which we classified them as either "Large" or "Small" dopamine neurons), the Large dopamine neurons produced more action potentials in response to weak current stimuli, while the Small neurons only produced a more phasic/single spiking response to these stimuli (Korshunov et al, 2020). When stimulated with stronger current stimuli, the Large and Small neurons both produced the same phasic/single spiking response (Korshunov et al, 2020).…”

“…Both OSNs (Berkowicz et al, 1994;Ennis et al, 1996) and M/TCs (Trombley and Westbrook, 1990) release glutamate at these synapses. However, subsequent findings indicated that TH expression is also present in layers deep to the GL, including the EPL, MCL, and GCL (Baker et al, 2001;Pignatelli et al, 2009;Kosaka et al, 2019;Korshunov et al, 2020). There is no conclusive finding to explain why TH expression can occur deep to the GL, but Pignatelli et al (2009) had found that even ∼75% of the deep (in the EPL) TH green fluorescent protein (GFP) neurons are capable of responding to OSN stimulation.…”

“…We recently published findings on the biophysical properties of rat OB dopamine neurons, and described how these properties may distinguish different groups of dopamine neurons (as was discussed in section "Olfactory Bulb Dopamine Neurons") (Korshunov et al, 2020). Similar to previous work in mice, we used a transgenic rat model (Iacovitti et al, 2014) with dopamine neurons that expressed a fluorescent protein to easily target cells.…”

“…A weak odor or artificial stimulus is hypothesized to activate dopamine neurons (blue neurons), while a strong odor stimulus is hypothesized to inactivate dopamine neurons (Ennis et al, 2001;Korshunov et al, 2020). In our previous work (Korshunov et al, 2020), we showed that rat olfactory bulb dopamine neurons are more responsive (produced more action potentials) to weak rather than strong current stimuli, potentially increasing the release of dopamine and/or GABA, resulting in presynaptic inhibition (McGann, 2013). Dopamine activity within fish olfactory bulbs was shown to reduce the transmission of weak stimuli while strong stimuli were processed more than weak stimuli (Bundschuh et al, 2012).…”