Sensory input reaching the brain from bilateral and offset channels is nonetheless perceived as unified. This unity could be explained by simultaneous projections to both hemispheres, or inter-hemispheric information transfer between sensory cortical maps. Odor input, however, is not topographically organized, nor does it project bilaterally, making olfactory perceptual unity enigmatic. Here we report a circuit that interconnects mirror-symmetric isofunctional mitral/tufted cells between the mouse olfactory bulbs. Connected neurons respond to similar odors from ipsi- and contra-nostrils, whereas unconnected neurons do not respond to odors from the contralateral nostril. This connectivity is likely mediated through a one-to-one mapping from mitral/tufted neurons to the ipsilateral anterior olfactory nucleus pars externa, which activates the mirror-symmetric isofunctional mitral/tufted neurons glutamatergically. This circuit enables sharing of odor information across hemispheres in the absence of a cortical topographical organization, suggesting that olfactory glomerular maps are the equivalent of cortical sensory maps found in other senses.
The entopeduncular nucleus (EP) is one of the basal ganglia output nuclei integrating synaptic information from several pathways within the basal ganglia. The firing of EP neurons is modulated by two streams of inhibitory synaptic transmission, the direct pathway from the striatum and the indirect pathway from the globus pallidus. These two inhibitory pathways continuously modulate the firing of EP neurons. However, the link between these synaptic inputs to neuronal firing in the EP is unclear. To investigate this input-output transformation we performed whole-cell and perforated-patch recordings from single neurons in the entopeduncular nucleus in rat brain slices during repetitive stimulation of the striatum and the globus pallidus at frequencies within the in vivo activity range of these neurons. These recordings, supplemented by compartmental modelling, showed that GABAergic synapses from the striatum, converging on EP dendrites, display short-term facilitation and that somatic or proximal GABAergic synapses from the globus pallidus show short-term depression. Activation of striatal synapses during low presynaptic activity decreased postsynaptic firing rate by continuously increasing the inter-spike interval. Conversely, activation of pallidal synapses significantly affected postsynaptic firing during high presynaptic activity. Our data thus suggest that low-frequency striatal output may be encoded as progressive phase shifts in downstream nuclei of the basal ganglia while high-frequency pallidal output may continuously modulate EP firing.
Dopamine is known to differentially modulate the impact of cortical input to the striatum between the direct and indirect pathways of the basal ganglia (BG). However, the role of extrastriatal dopamine receptors (DRs) in BG information processing is less clear. To investigate the role of extrastriatal DRs, we studied their distribution and function in one of the output nuclei of the BG of the rodent, the entopeduncular nucleus (EP). qRT-PCR indicated that all DR subtypes were expressed by EP neurons, suggesting that both D 1 -like receptors (D1LRs) and D 2 -like receptors (D2LRs) were likely to affect information processing in the EP. Whole-cell recordings revealed that striatal inputs to the EP were potentiated by D1LRs whereas pallidal inputs to the EP were depressed by D2LRs. Changes to the paired-pulse ratio of inputs to the EP suggested that dopaminergic modulation of striatal inputs is mediated by postsynaptic receptors, and that of globus pallidus-evoked inputs is mediated by presynaptic receptors. We show that these changes in synaptic efficacy changed the information content of EP neuron firing. Overall, the findings suggest that the dopaminergic system affects the passage of feedforward information through the BG by modulating input divergence in the striatum and output convergence in the EP.
The hyperdirect pathway of the basal ganglia bypasses the striatum, and delivers cortical information directly to the subthalamic nucleus (STN). In rodents, the STN excites the two output nuclei of the basal ganglia, the entopeduncular nucleus (EP) and the substantia nigra reticulata (SNr). Thus, during hyperdirect pathway activation, the STN drives EP firing inhibiting the thalamus. We hypothesized that STN activity could induce long-term changes to the STN->EP synapse. To test this hypothesis, we recorded in the whole-cell mode from neurons in the EP in acute brain slices from rats while electrically stimulating the STN. Repetitive pre-synaptic stimulation generated modest long-term depression (LTD) in the STN->EP synapse. However, pairing EP firing with STN stimulation generated robust LTD that manifested for pre-before post-as well as for post- before pre-synaptic pairing. This LTD was highly sensitive to the time difference and was not detected at a time delay of 10 ms. To investigate whether post-synaptic calcium levels were important for LTD induction, we made dendritic recordings from EP neurons that revealed action potential back-propagation and dendritic calcium transients. Buffering the dendritic calcium concentration in the EP neurons with EGTA generated long term potentiation instead of LTD. Finally, mild LTD could be induced by post-synaptic activity alone that was blocked by an endocannabinoid 1 (CB1) receptor blocker. These results thus suggest there may be an adaptive mechanism for buffering the impact of the hyperdirect pathway on basal ganglia output which could contribute to the de-correlation of STN and EP firing.
Dopamine is critical for the normal functioning of the basal ganglia, modulating both input and output nuclei of this system. The distribution and function of each of the five dopamine receptor subtypes have been studied extensively in the striatum. However, the role of extrastriatal dopamine receptors in basal ganglia information processing is less clear. Here, we studied the anatomical distribution of dopamine receptors in one of the output nuclei of the rodent basal ganglia, the entopeduncular nucleus (EP). The presence of all dopamine receptor subtypes was verified in the EP using immunostaining. We detected co-localization of dopamine receptors with VGAT, which suggests presynaptic expression on GABAergic terminals. D1R and D2R were strongly colocalized with VGAT, whereas DR3-5 showed only sparse co-localization. We further labeled striatal or pallidal neurons with GFP and showed that only D1 receptors were co-localized with striatal terminals, while only D2R and D3R were co-localized with pallidal terminals. Dopamine receptors were also strongly co-localized with MAP2, indicating postsynaptic expression. Overall, these findings suggest that the dopaminergic system modulates activity in the EP both directly via postsynaptic receptors, and indirectly via GABAergic synapses stemming from the direct and indirect pathways.
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