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How reduction of theta rhythm by medial septum inactivation may covary with disruption of entorhinal grid cell responses due to reduced cholinergic transmission.

Pilly PK, Grossberg S - Front Neural Circuits (2013)

Bottom Line: Two recent studies reduced the theta rhythm by inactivating the medial septum (MS) and demonstrated a correlated reduction in the characteristic hexagonal spatial firing patterns of grid cells.In particular, the adverse effects of MS inactivation on grid cells can be understood in terms of how the concomitant reduction in cholinergic inputs may increase the conductances of leak potassium (K(+)) and slow and medium after-hyperpolarization (sAHP and mAHP) channels.These results demonstrate how models of grid cell self-organization can provide new insights into the relationship between brain learning and oscillatory dynamics.

View Article: PubMed Central - PubMed

Affiliation: Center for Neural and Emergent Systems, Information and Systems Sciences Laboratory, HRL Laboratories Malibu, CA, USA.

ABSTRACT
Oscillations in the coordinated firing of brain neurons have been proposed to play important roles in perception, cognition, attention, learning, navigation, and sensory-motor control. The network theta rhythm has been associated with properties of spatial navigation, as has the firing of entorhinal grid cells and hippocampal place cells. Two recent studies reduced the theta rhythm by inactivating the medial septum (MS) and demonstrated a correlated reduction in the characteristic hexagonal spatial firing patterns of grid cells. These results, along with properties of intrinsic membrane potential oscillations (MPOs) in slice preparations of medial entorhinal cortex (MEC), have been interpreted to support oscillatory interference models of grid cell firing. The current article shows that an alternative self-organizing map (SOM) model of grid cells can explain these data about intrinsic and network oscillations without invoking oscillatory interference. In particular, the adverse effects of MS inactivation on grid cells can be understood in terms of how the concomitant reduction in cholinergic inputs may increase the conductances of leak potassium (K(+)) and slow and medium after-hyperpolarization (sAHP and mAHP) channels. This alternative model can also explain data that are problematic for oscillatory interference models, including how knockout of the HCN1 gene in mice, which flattens the dorsoventral gradient in MPO frequency and resonance frequency, does not affect the development of the grid cell dorsoventral gradient of spatial scales, and how hexagonal grid firing fields in bats can occur even in the absence of theta band modulation. These results demonstrate how models of grid cell self-organization can provide new insights into the relationship between brain learning and oscillatory dynamics.

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Model simulation of the MS inactivation data by reduced cholinergic transmission (Cases 5–7). Simulations of temporary reductions in gridness score (A,D), mean firing rate (B,E), and spatial stability (C,F), respectively, of model grid cells as a result of abrupt changes in leak conductances and habituation rates for one trial. The two columns correspond to the two entorhinal SOMs, which learn to encode two different grid scales of spatial representation. As in panels (B) and (C) of Figure 1, the arrow in each panel signifies MS inactivation. The legend for the various colored plots is provided in panel (C). The various measures are shown for model grid cells with a gridness score > 0 in the trial immediately preceding the one coinciding with the inactivated MS. Error bars in all panels indicate SEM.
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Figure 9: Model simulation of the MS inactivation data by reduced cholinergic transmission (Cases 5–7). Simulations of temporary reductions in gridness score (A,D), mean firing rate (B,E), and spatial stability (C,F), respectively, of model grid cells as a result of abrupt changes in leak conductances and habituation rates for one trial. The two columns correspond to the two entorhinal SOMs, which learn to encode two different grid scales of spatial representation. As in panels (B) and (C) of Figure 1, the arrow in each panel signifies MS inactivation. The legend for the various colored plots is provided in panel (C). The various measures are shown for model grid cells with a gridness score > 0 in the trial immediately preceding the one coinciding with the inactivated MS. Error bars in all panels indicate SEM.

Mentions: Simulation results are presented in Figures 3–9. We first replicated the main finding of Grossberg and Pilly (2012) that faster response rates (μm) of entorhinal map cells cause them to develop hexagonal grid firing fields that are formed from appropriate combinations of stripe cells with the smaller of the input scales, and vice versa (see Figure 3). We then found that temporary reductions in response rates, or rates of temporal integration, can indeed disrupt the expression of learned periodic spatial fields of grid cells by way of delayed and reduced firing with longer refractory periods. Model grid cells are shown to exhibit lower gridness scores, mean firing rates, and spatial stability values during this period in proportion to divisive reductions in response rates; namely, half, one-fourth, and one-eighth (see Figure 4). These results can be understood as direct consequences of reductions in the expected firing for each grid cell at its grid positions due to decreased excitability combined with increased refraction, and also of increased likelihoods for each cell to become activated in non-preferred positions due to lack of expected inhibition from other cells that are activated only weakly if at all.


How reduction of theta rhythm by medial septum inactivation may covary with disruption of entorhinal grid cell responses due to reduced cholinergic transmission.

Pilly PK, Grossberg S - Front Neural Circuits (2013)

Model simulation of the MS inactivation data by reduced cholinergic transmission (Cases 5–7). Simulations of temporary reductions in gridness score (A,D), mean firing rate (B,E), and spatial stability (C,F), respectively, of model grid cells as a result of abrupt changes in leak conductances and habituation rates for one trial. The two columns correspond to the two entorhinal SOMs, which learn to encode two different grid scales of spatial representation. As in panels (B) and (C) of Figure 1, the arrow in each panel signifies MS inactivation. The legend for the various colored plots is provided in panel (C). The various measures are shown for model grid cells with a gridness score > 0 in the trial immediately preceding the one coinciding with the inactivated MS. Error bars in all panels indicate SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814006&req=5

Figure 9: Model simulation of the MS inactivation data by reduced cholinergic transmission (Cases 5–7). Simulations of temporary reductions in gridness score (A,D), mean firing rate (B,E), and spatial stability (C,F), respectively, of model grid cells as a result of abrupt changes in leak conductances and habituation rates for one trial. The two columns correspond to the two entorhinal SOMs, which learn to encode two different grid scales of spatial representation. As in panels (B) and (C) of Figure 1, the arrow in each panel signifies MS inactivation. The legend for the various colored plots is provided in panel (C). The various measures are shown for model grid cells with a gridness score > 0 in the trial immediately preceding the one coinciding with the inactivated MS. Error bars in all panels indicate SEM.
Mentions: Simulation results are presented in Figures 3–9. We first replicated the main finding of Grossberg and Pilly (2012) that faster response rates (μm) of entorhinal map cells cause them to develop hexagonal grid firing fields that are formed from appropriate combinations of stripe cells with the smaller of the input scales, and vice versa (see Figure 3). We then found that temporary reductions in response rates, or rates of temporal integration, can indeed disrupt the expression of learned periodic spatial fields of grid cells by way of delayed and reduced firing with longer refractory periods. Model grid cells are shown to exhibit lower gridness scores, mean firing rates, and spatial stability values during this period in proportion to divisive reductions in response rates; namely, half, one-fourth, and one-eighth (see Figure 4). These results can be understood as direct consequences of reductions in the expected firing for each grid cell at its grid positions due to decreased excitability combined with increased refraction, and also of increased likelihoods for each cell to become activated in non-preferred positions due to lack of expected inhibition from other cells that are activated only weakly if at all.

Bottom Line: Two recent studies reduced the theta rhythm by inactivating the medial septum (MS) and demonstrated a correlated reduction in the characteristic hexagonal spatial firing patterns of grid cells.In particular, the adverse effects of MS inactivation on grid cells can be understood in terms of how the concomitant reduction in cholinergic inputs may increase the conductances of leak potassium (K(+)) and slow and medium after-hyperpolarization (sAHP and mAHP) channels.These results demonstrate how models of grid cell self-organization can provide new insights into the relationship between brain learning and oscillatory dynamics.

View Article: PubMed Central - PubMed

Affiliation: Center for Neural and Emergent Systems, Information and Systems Sciences Laboratory, HRL Laboratories Malibu, CA, USA.

ABSTRACT
Oscillations in the coordinated firing of brain neurons have been proposed to play important roles in perception, cognition, attention, learning, navigation, and sensory-motor control. The network theta rhythm has been associated with properties of spatial navigation, as has the firing of entorhinal grid cells and hippocampal place cells. Two recent studies reduced the theta rhythm by inactivating the medial septum (MS) and demonstrated a correlated reduction in the characteristic hexagonal spatial firing patterns of grid cells. These results, along with properties of intrinsic membrane potential oscillations (MPOs) in slice preparations of medial entorhinal cortex (MEC), have been interpreted to support oscillatory interference models of grid cell firing. The current article shows that an alternative self-organizing map (SOM) model of grid cells can explain these data about intrinsic and network oscillations without invoking oscillatory interference. In particular, the adverse effects of MS inactivation on grid cells can be understood in terms of how the concomitant reduction in cholinergic inputs may increase the conductances of leak potassium (K(+)) and slow and medium after-hyperpolarization (sAHP and mAHP) channels. This alternative model can also explain data that are problematic for oscillatory interference models, including how knockout of the HCN1 gene in mice, which flattens the dorsoventral gradient in MPO frequency and resonance frequency, does not affect the development of the grid cell dorsoventral gradient of spatial scales, and how hexagonal grid firing fields in bats can occur even in the absence of theta band modulation. These results demonstrate how models of grid cell self-organization can provide new insights into the relationship between brain learning and oscillatory dynamics.

Show MeSH
Related in: MedlinePlus