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Ramirez-Gordillo, D.

Publications and source records attributed to Ramirez-Gordillo, D..

4 recordsLinked to original sources

Connexin 36-mediated gap junctions contribute to fine odor discrimination and excitation of mitral cells in the mouse olfactory bulb

Key PointsO_LIThe output MCs of the olfactory bulb (OB) engage in strong electrical coupling via connexin 36 (Cx36)-mediated gap junctions. However, the behavioral and physiological relevance of these gap junctions is not well understood. C_LIO_LIIn studies conducted in Cx36 knock-out (KO) mice, we found that the mice displayed reduced fine odor discrimination capabilities versus wild-type mice in a go/no-go associative learning task. These results provide the first evidence to date of olfactory behavioral deficits in Cx36 KO mice. C_LIO_LIIn OB slices, Cx36 KO reduced excitatory responses in MCs to electrical stimulation of sensory afferents, especially during latter stages of the response. C_LIO_LIWe suggest that KO-induced impairments in fine odor discrimination are linked to reduced late MC excitation due to the longer time that mice require to make difficult odor discriminations. C_LI The output mitral cells (MCs) and tufted cells (TCs) of the mammalian olfactory bulb (OB) are coupled through both chemical mechanisms as well as gap junctions that are mediated by connexin 36 (Cx36). Here we tested both behavioral and physiological effects of eliminating gap junctions in knockout (KO) mice with homozygous deletions of Cx36. In a go/no-go associative learning task, Cx36 KO mice were found to display reduced discrimination capabilities when presented with pairs of stimuli that included a monomolecular odor and mixtures that had the same monomolecular odor and a small amount of a structurally similar odor. The impairments did not occur for less similar odor pairs, suggesting that Cx36 KO mice have olfactory processing deficits that are specific to fine odor discrimination. In physiological recordings in OB slices from Cx36 KO mice, MCs displayed reduced excitation in response to electrical stimulation of sensory afferents, both single stimulus pulses as well as a theta burst pattern designed to mimic sniffing. The reduction in MC excitatory current was most prominent for late portions of their response, 300 ms after single stimulus pulses or following all theta bursts that came after the first. More global local field potentials recorded in OB glomeruli were largely unaffected by Cx36 KO. We suggest that the KO-induced impairments in fine odor discrimination are linked to reduced late MC excitation due to the longer time that mice require to make difficult odor discriminations.

neuroscience↗

GRINtrode: A neural implant for simultaneous two-photon imaging and extracellular electrophysiology in freely moving animals

SignificanceIn vivo imaging and electrophysiology are powerful tools to explore neuronal function that each offer unique complementary information with advantages and limitations. Capturing both data types from the same neural population in the freely moving animal would allow researchers to take advantage of the capabilities of both modalities and further understand how they relate to each other. AimHere we present a head-mounted neural implant suitable for in vivo two-photon imaging of neuronal activity with simultaneous extracellular electrical recording in head-fixed or freely moving animals. ApproachA GRIN lens-based head-mounted neural implant with extracellular electrical recording provided by tetrodes on the periphery of the GRIN lens was chronically implanted. The design of the neural implant allows for recording from head-fixed animals, as well as freely moving animals by coupling the imaging system to a coherent imaging fiber bundle. ResultsWe demonstrate simultaneous two-photon imaging of GCaMP and extracellular electrophysiology of neural activity in awake head-fixed, and freely moving mice. Using the collected information, we perform correlation analysis to reveal positive correlation between optical and local field potential recordings. ConclusionSimultaneously recording neural activity using both optical and electrical methods provides complementary information from each modality. Designs that can provide such bimodal recording in freely moving animals allow for the investigation of neural activity underlying a broader range of behavioral paradigms.

neuroscience↗

Hippocampal-prefrontal theta coupling develops as mice become proficient in associative odorant discrimination learning

Learning and memory requires coordinated activity between different regions of the brain. Here we studied the interaction between infralimbic medial prefrontal cortex (mPFC) and hippocampal dorsal CA1 during associative odorant discrimination learning in the male mouse. We found that as the animal learns to discriminate odorants in a go- no go task the coupling of high frequency neural oscillations to the phase of theta oscillations (theta-referenced phase-amplitude coupling or tPAC) changes in a manner that results in divergence between rewarded and unrewarded odorant-elicited changes in the theta-phase referenced power (tPRP) for beta and gamma oscillations. In addition, in the proficient animal there was a decrease in the coordinated oscillatory activity between CA1 and mPFC in the presence of the unrewarded odorant. Furthermore, the changes in tPAC resulted in a marked increase in the accuracy for decoding contextual odorant identity from tPRP when the animal became proficient. Finally, we studied the role of Ca2+/calmodulin-dependent protein kinase II (CaMKII), a protein involved in learning and memory, in oscillatory neural processing in this task. We find that the accuracy for decoding the contextual odorant identity from tPRP decreases in CaMKII knockout mice and that this accuracy correlates with behavioral performance. These results implicate a role for tPAC and CaMKII genotype in olfactory go-no go associative learning in the hippocampal-prefrontal circuit. Significance statementCoupling of neural oscillations between hippocampal CA1 and medial prefrontal cortex (mPFC) is involved in spatial learning and memory, but the role of oscillation coupling for other learning tasks is not well understood. Here we performed local field potential recording in CA1 and mPFC in mice learning to differentiate rewarded from unrewarded odorants in an associative learning task. We find that odorant-elicited changes in the power of bursts of gamma oscillations at distinct phases of theta oscillations become divergent as the animal becomes proficient allowing decoding of contextual odorant identity. Finally, we find that the accuracy to decode contextual odorant identity decreases in mice deficient for the expression of Ca2+/calmodulin-dependent protein kinase II , a protein involved in synaptic plasticity.

neuroscience↗

Learning improves decoding of odor identity with phase-referenced oscillations in the olfactory bulb

Local field potential oscillations reflect temporally coordinated neuronal ensembles-- coupling distant brain regions, gating processing windows, and providing a reference for spike timing-based codes. In phase amplitude coupling (PAC), the amplitude of the envelope of a faster oscillation is larger within a phase window of a slower carrier wave. Here, we characterized PAC, and the related theta phase-referenced high gamma and beta power (PRP), in the olfactory bulb of mice learning to discriminate odorants. PAC changes throughout learning, and odorant-elicited changes in PRP increase for rewarded and decrease for unrewarded odorants. Contextual odorant identity (is the odorant rewarded?) can be decoded from peak PRP in animals proficient in odorant discrimination, but not in naive mice. As the animal learns to discriminate the odorants the dimensionality of PRP decreases. Therefore, modulation of phase-referenced chunking of information in the course of learning plays a role in early sensory processing in olfaction. SignificanceEarly processing of olfactory information takes place in circuits undergoing slow frequency theta oscillations generated by the interplay of olfactory input modulated by sniffing and centrifugal feedback from downstream brain areas. Studies in the hippocampus and cortex suggest that different information "chunks" are conveyed at different phases of the theta oscillation. Here we show that in the olfactory bulb, the first processing station in the olfactory system, the amplitude of high frequency gamma oscillations encodes for information on whether an odorant is rewarded when it is observed at the peak phase of the theta oscillation. Furthermore, encoding of information by the theta phase-referenced gamma oscillations becomes more accurate as the animal learns to differentiate two odorants.

neuroscience↗