Investigation of the hippocampal information processing in freely moving rats

Azahara Gonzalez Oliva
Investigation of the hippocampal information processing in freely moving rats.
Doktori értekezés, Szegedi Tudományegyetem.

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Extracellular electrophysiological recordings of the hippocampus were carried out in freely moving Long-Evans rats. Large-scale and high-density electrodes were used to target all subregions simultaneously. We were able to record both local field potentials (LFPs) and single unit activity, which allowed for the analysis of population activity and individual cells, respectively. We recorded the animals while they performed spatial navigational tasks and during sleep in their home cages. We focused our investigations on the information processing of the hippocampus during its two main general functions: spatial navigation and memory consolidation. In particular, two main questions were addressed in this work:How the different subregions of the hippocampus contribute to spatial coding within the hippocampus. How the distinct subregions of the hippocampus coordinate to generate sharp-wave ripples complexes, known to be essential in memory consolidation To investigate the contribution of the different subregions of the hippocampus to spatial coding, we recorded simultaneously place cells (neurons which selectively respond to crossing locations in the environment) from CA1, CA2 and CA3 during spatial navigation.We analized the fine function of the distinct anatomical portions of these areas separating CA1 into proximal, intermediate and distal and CA3 into CA3c, CA3b and CA3a subregions.We could also record neurons located at several depths of the soma layers so we treated the deep (toward stratum oriens) and the superficially (toward stratum radiatum) located cells inthe CA1, CA2 and CA3 regions separately. We analyzed the distinct properties of the place cells located in the different subregions and found significant differences which characterize the spatial coding in these parts and correlate with the anatomy. The CA1 and CA2 regions in general had a higher number of place cells than the CA3region. Furthermore, more fields per cell were found in CA1 neurons and CA2 compared to their CA3 peers. Firing rates inside the fields and peak firing rates were also higher for CA1 and CA2. The more spatially informative place cells were the ones located in CA3, and the less informative the CA2 ones. Inside the different subregions, CA1 proximal cells appeared 43 to be more spatially informative, showed higher firing rates in-field and a tended to have one single place field whereas toward CA1 distal they fired less, had more place fields and contained less spatial information. For the CA3 region, more spatially informative and selective place cells were located in CA3c, with preferentially single fields but lower firing rates than in their CA3a peers. No significant differences were found within the cells located at different depths in the CA3 area, whereas in CA1 and CA2 a tendency characterized the deep cells with more number of place cells, higher in-field firing rates but less selective and spatially informative than their superficial peers. These findings are in correlation with the axonal distribution of the different afferents to the hippocampus, mainly from the entorhinal cortex. The medial part of the entorhinal cortex (where the highly spatially selective grid cells are located) is preferentially connected with the proximal CA1 (more spatial selectivity than the distal part) and the lateral portion of the entorhinal cortex (where mainly object and environmental cues coding cells are located) mainly target the distal part of CA1 (more place fields per cell and less spatially informative). Unlike the CA1, cells in the CA3 region have strong recurrent collaterals, which can account for the lower number and highly spatially selective place cells in this region. The least informative cells during spatial navigation were the ones located in CA2, which is in line with the discovery of a specific network which code for space during immobility inside this region. The phase precession was weaker in place cells from the CA2 region, which can be also explained by the distinct combination of inputs arriving to this part of the hippocampus. The theta phase locking of the different subregions also correlates with anatomical inputs. While a relatively preserved phase preference was found in CA1 cells from all subregions during RUN (ascending phase of the cycle), a gradual shift was notable from the CA2-CA3a border (ascending phase) toward the CA3c (descending phase). During REM, an important percentage of cells shift their firing with 180º in the CA1 region, but this is not the case for the cells located in CA2 or CA3 regions. Therefore, this is assumed to be related to the specific entorhinal layer III input to the CA1 region. To investigate the generation and propagation of sharp-wave-ripple (SPW-Rs) complexes we detected these population events in all hippocampal regions (CA1, CA2 and CA3). We found that ripples detected in the different subregions can generate different current source density (CSD) and local field potentials (LFP) patterns in the CA1 region. The 44 CA3 initiated events gave rise to characteristic CSD pattern with a sink in stratum radiatum (due to the input from the Schaffer collaterals axons into the CA1 population) and two sources surrounding it (output of currents through the soma and lacunosum-moleculare layer). In the LFP this is visible as a slow negative sharp-wave in the stratum radiatum of CA1 and the high frequency oscillation (‘ripple’, 150-240 Hz) generated by the synchronization of the pyramidal-interneurons spiking activity. However, the CA2 initiated events generate an additional CSD-LFP pattern characterized by a sink with the corresponding slow wave in the stratum oriens of CA1, confirming the direct transmission of information from CA2 to CA1. This later pattern was found to be dominant during awake states, supporting the specific role of the CA2 region during awake immobility. We then examined the contribution of single pyramidal cells to SPW-Rs detected in CA1. We found that although the vast majority of pyramidal neurons located in CA1 and CA3 respond with an excitation (increasing their firing rate) to SPW-Rs, in the CA2 region two equally large subpopulations exist. One showed positive (phasic cells) and the other one showed negative modulation during ripples (ripple-ramping cells, decreasing their firing rate).We also found that the ripple-ramping cell population shows a preceding slow excitation prior to inhibition that coincides with SPW-R events. This pattern is followed by the phasic neurons (also in the CA2 region) and then by the propagation to the CA3a, CA3b, CA3c, and finally CA1 population of cells. We then detected ripples in the CA2 region and study again the firing dynamics of all pyramidal subpopulations. We found that the two subpopulations distinguished in the CA2 region, ramping and phasic cells, identically increased their firing rates during local ripples. The first population in the temporal sequence of response was still the CA2 ramping cells group, followed by the CA2 phasic, and then CA3 subregions and CA1. These results prompt to the CA2 region as a potential trigger of SPW-Rs in the hippocampus.The SPW-Rs events show a very clear increase in power of the corresponding frequency band (150-240 Hz) in the LFP. We tested the spatio-temporal response of the distinct subregions during SPW-Rs in the time-frequency domain. The CA2 region increased the ripple-band frequency power earlier than any other, followed by CA3 and CA1. We concluded then that the first region becoming active before SPW-Rs events was the CA2 particularly, ripple-ramping neurons, which then became silent when the ripples reached the 45 CA1 region. The next group of cells becoming active was the CA2 phasic neurons group, followed by the CA3a, CA3b, CA3c and finally the CA1 neurons. These results show a clear pattern of propagation of local excitation in time, from CA2 to CA3 and to CA1, which correlate with the known anatomy. This was observed during both states, SLEEP and WAKE. However, during the WAKE state the onset of the CA2 subpopulations was even earlier than the SPW-R triggers in CA1. Also, during WAKE state but not running periods, CA2 pyramidal neurons showed a very high firing rate. These results together with the earlier timing during WAKE state can be related with the specific network which code for immobility, recently found to be located in the CA2 region. Different functional characteristics were already attributed to the CA1 cells located in deep and in superficial layers. Then, we investigated whether the two functional subpopulations we found in the CA2 have also distinct anatomical locations. We found that deep CA2 pyramidal neurons and superficial CA2 pyramidal neurons correlate with the firing dynamics of the CA2 ripple-ramping and CA2 phasic groups, respectively. We show a significant segregation of the location of the ramping cells toward deep layers and the phasic cells toward superficial layers of the immunolabeled CA2 region. This anatomical segregation of the two different types of cells together with the role of CA2 during SPW-Rs could be explained by the unique anatomical wiring of this region compared to the neighboring areas, CA1 and CA3.

Mű típusa: Disszertáció (Doktori értekezés)
Doktori iskola: Elméleti Orvostudományok Doktori Iskola
Tudományterület / tudományág: orvostudományok > elméleti orvostudományok
Magyar cím: A hippokampális információ feldolgozás vizsgálata szabadon mozgó patkányban
Idegen nyelvű cím: Investigation of the hippocampal information processing in freely moving rats
Témavezető neveBeosztás, tudományos fokozat, intézményEmail
Dr. Berényi AntalPhD SZTE ÁOK Élettani Inté
EPrint azonosító (ID): 3145
Publikációban használt név : Azahara Gonzalez Oliva
A mû MTMT azonosítója: 3195443
doi: 10.14232/phd.3145
A feltöltés ideje: 2016. okt. 12. 15:53
Utolsó módosítás: 2017. márc. 03. 10:04
Egyebek (raktári szám): B 6090
Védés állapota: védett

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