Limits...
Involvement of the GABAergic septo-hippocampal pathway in brain stimulation reward.

Vega-Flores G, Gruart A, Delgado-García JM - PLoS ONE (2014)

Bottom Line: The successive BSR sessions evoked a progressive increase of the performance in inverse relationship with a decrease in the amplitude of fEPSPs, but not of fIPSPs.We corroborate a clear preference for BSR at 100 Hz (in comparison with BSR at 20 Hz or 8 Hz), in parallel with an increase in the spectral power of the low theta band, and a decrease in the gamma.These results were replicated by intrahippocampal injections of a GABAB antagonist.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurosciences, Pablo de Olavide University, Seville, Spain.

ABSTRACT
The hippocampus is a structure related to several cognitive processes, but not very much is known about its putative involvement in positive reinforcement. In its turn, the septum has been related to instrumental brain stimulation reward (BSR) by its electrical stimulation with trains of pulses. Although the anatomical relationships of the septo-hippocampal pathway are well established, the functional relationship between these structures during rewarding behaviors remains poorly understood. To explore hippocampal mechanisms involved in BSR, CA3-evoked field excitatory and inhibitory postsynaptic potentials (fEPSPs, fIPSPs) were recorded in the CA1 area during BSR in alert behaving mice. The synaptic efficiency was determined from changes in fEPSP and fIPSP amplitudes across the learning of a BSR task. The successive BSR sessions evoked a progressive increase of the performance in inverse relationship with a decrease in the amplitude of fEPSPs, but not of fIPSPs. Additionally, we evaluated CA1 local field potentials (LFPs) during a preference task, comparing 8-, 20-, and 100-Hz trains of septal BSR. We corroborate a clear preference for BSR at 100 Hz (in comparison with BSR at 20 Hz or 8 Hz), in parallel with an increase in the spectral power of the low theta band, and a decrease in the gamma. These results were replicated by intrahippocampal injections of a GABAB antagonist. Thus, the GABAergic septo-hippocampal pathway seems to carry information involved in the encoding of reward properties, where GABAB receptors seem to play a key role. With regard to the dorsal hippocampus, fEPSPs evoked at the CA3-CA1 synapse seem to reflect the BSR learning process, while hippocampal rhythmic activities are more related to reward properties.

Show MeSH
Acquisition of the BSR protocol and changes evoked in fPSPs.(A) Animals' performance was computed as (number of reinforcements obtained)/(maximum number of available reinforcements) x 100. Data for each mouse (n = 30) were arranged according to their own zero point, labeled as day “0”. Shaping and BSR are indicated by brown or orange edges, respectively. (B) Representative averages (10 times) of fPSPs recorded on three different days during the learning process of BSR. Illustrated fPSPs correspond to the shaping stage (1), the day when animals reached BSR criterion (2), and eight days after BSR criterion was reached (3). White arrows indicate stimulation of the CA3 area (St.). The horizontal black bar indicates a fragment of medial septum stimulation. BL, baseline; SB, recording inside the Skinner box. (C) Changes in fEPSP components across training (n = 28). The polynomial trend lines for the amplitude of fEPSP (or GLU) during shaping and BSR stages are indicated. Statistical comparisons are indicated vs. BL values (horizontal dashed line in 100%). (D) Changes in fIPSP components across training (n = 28). The polynomial trend lines for the amplitude of GABAB component during shaping and BSR stages are indicated. Statistical comparisons are indicated vs. BL values (dashed line in 100%). (*) P<0.05; (**) P<0.01; (***) P<0.001. Code bars at the top in each section are defined in Figure 1.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4263242&req=5

pone-0113787-g002: Acquisition of the BSR protocol and changes evoked in fPSPs.(A) Animals' performance was computed as (number of reinforcements obtained)/(maximum number of available reinforcements) x 100. Data for each mouse (n = 30) were arranged according to their own zero point, labeled as day “0”. Shaping and BSR are indicated by brown or orange edges, respectively. (B) Representative averages (10 times) of fPSPs recorded on three different days during the learning process of BSR. Illustrated fPSPs correspond to the shaping stage (1), the day when animals reached BSR criterion (2), and eight days after BSR criterion was reached (3). White arrows indicate stimulation of the CA3 area (St.). The horizontal black bar indicates a fragment of medial septum stimulation. BL, baseline; SB, recording inside the Skinner box. (C) Changes in fEPSP components across training (n = 28). The polynomial trend lines for the amplitude of fEPSP (or GLU) during shaping and BSR stages are indicated. Statistical comparisons are indicated vs. BL values (horizontal dashed line in 100%). (D) Changes in fIPSP components across training (n = 28). The polynomial trend lines for the amplitude of GABAB component during shaping and BSR stages are indicated. Statistical comparisons are indicated vs. BL values (dashed line in 100%). (*) P<0.05; (**) P<0.01; (***) P<0.001. Code bars at the top in each section are defined in Figure 1.

Mentions: Shaping sessions were followed by several BSR sessions (Figures 1C, D and 2). These were organized as described for shaping sessions, but in this case, train stimulation of the medial septum was carried out only when the animal pressed the lever of its own accord. Figure 2 summarizes the learning process from shaping until BSR. During both shaping and BSR stages, reinforcements could be received at a maximum rate of one/5 s - i.e., with the same fixed-time-interval schedule (FI5). We decided to use this schedule to rule out paired-pulse facilitation effects on the recorded fPSPs. A specific test was carried out to verify this in 7 animals. A single pulse was delivered automatically in the CA3 area every 5 s for more than 30 min to simulate the highest activation of the CA3-CA1 synapse during BSR. The amplitude of the fEPSP was unchanged across this test (P<0.952).


Involvement of the GABAergic septo-hippocampal pathway in brain stimulation reward.

Vega-Flores G, Gruart A, Delgado-García JM - PLoS ONE (2014)

Acquisition of the BSR protocol and changes evoked in fPSPs.(A) Animals' performance was computed as (number of reinforcements obtained)/(maximum number of available reinforcements) x 100. Data for each mouse (n = 30) were arranged according to their own zero point, labeled as day “0”. Shaping and BSR are indicated by brown or orange edges, respectively. (B) Representative averages (10 times) of fPSPs recorded on three different days during the learning process of BSR. Illustrated fPSPs correspond to the shaping stage (1), the day when animals reached BSR criterion (2), and eight days after BSR criterion was reached (3). White arrows indicate stimulation of the CA3 area (St.). The horizontal black bar indicates a fragment of medial septum stimulation. BL, baseline; SB, recording inside the Skinner box. (C) Changes in fEPSP components across training (n = 28). The polynomial trend lines for the amplitude of fEPSP (or GLU) during shaping and BSR stages are indicated. Statistical comparisons are indicated vs. BL values (horizontal dashed line in 100%). (D) Changes in fIPSP components across training (n = 28). The polynomial trend lines for the amplitude of GABAB component during shaping and BSR stages are indicated. Statistical comparisons are indicated vs. BL values (dashed line in 100%). (*) P<0.05; (**) P<0.01; (***) P<0.001. Code bars at the top in each section are defined in Figure 1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263242&req=5

pone-0113787-g002: Acquisition of the BSR protocol and changes evoked in fPSPs.(A) Animals' performance was computed as (number of reinforcements obtained)/(maximum number of available reinforcements) x 100. Data for each mouse (n = 30) were arranged according to their own zero point, labeled as day “0”. Shaping and BSR are indicated by brown or orange edges, respectively. (B) Representative averages (10 times) of fPSPs recorded on three different days during the learning process of BSR. Illustrated fPSPs correspond to the shaping stage (1), the day when animals reached BSR criterion (2), and eight days after BSR criterion was reached (3). White arrows indicate stimulation of the CA3 area (St.). The horizontal black bar indicates a fragment of medial septum stimulation. BL, baseline; SB, recording inside the Skinner box. (C) Changes in fEPSP components across training (n = 28). The polynomial trend lines for the amplitude of fEPSP (or GLU) during shaping and BSR stages are indicated. Statistical comparisons are indicated vs. BL values (horizontal dashed line in 100%). (D) Changes in fIPSP components across training (n = 28). The polynomial trend lines for the amplitude of GABAB component during shaping and BSR stages are indicated. Statistical comparisons are indicated vs. BL values (dashed line in 100%). (*) P<0.05; (**) P<0.01; (***) P<0.001. Code bars at the top in each section are defined in Figure 1.
Mentions: Shaping sessions were followed by several BSR sessions (Figures 1C, D and 2). These were organized as described for shaping sessions, but in this case, train stimulation of the medial septum was carried out only when the animal pressed the lever of its own accord. Figure 2 summarizes the learning process from shaping until BSR. During both shaping and BSR stages, reinforcements could be received at a maximum rate of one/5 s - i.e., with the same fixed-time-interval schedule (FI5). We decided to use this schedule to rule out paired-pulse facilitation effects on the recorded fPSPs. A specific test was carried out to verify this in 7 animals. A single pulse was delivered automatically in the CA3 area every 5 s for more than 30 min to simulate the highest activation of the CA3-CA1 synapse during BSR. The amplitude of the fEPSP was unchanged across this test (P<0.952).

Bottom Line: The successive BSR sessions evoked a progressive increase of the performance in inverse relationship with a decrease in the amplitude of fEPSPs, but not of fIPSPs.We corroborate a clear preference for BSR at 100 Hz (in comparison with BSR at 20 Hz or 8 Hz), in parallel with an increase in the spectral power of the low theta band, and a decrease in the gamma.These results were replicated by intrahippocampal injections of a GABAB antagonist.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurosciences, Pablo de Olavide University, Seville, Spain.

ABSTRACT
The hippocampus is a structure related to several cognitive processes, but not very much is known about its putative involvement in positive reinforcement. In its turn, the septum has been related to instrumental brain stimulation reward (BSR) by its electrical stimulation with trains of pulses. Although the anatomical relationships of the septo-hippocampal pathway are well established, the functional relationship between these structures during rewarding behaviors remains poorly understood. To explore hippocampal mechanisms involved in BSR, CA3-evoked field excitatory and inhibitory postsynaptic potentials (fEPSPs, fIPSPs) were recorded in the CA1 area during BSR in alert behaving mice. The synaptic efficiency was determined from changes in fEPSP and fIPSP amplitudes across the learning of a BSR task. The successive BSR sessions evoked a progressive increase of the performance in inverse relationship with a decrease in the amplitude of fEPSPs, but not of fIPSPs. Additionally, we evaluated CA1 local field potentials (LFPs) during a preference task, comparing 8-, 20-, and 100-Hz trains of septal BSR. We corroborate a clear preference for BSR at 100 Hz (in comparison with BSR at 20 Hz or 8 Hz), in parallel with an increase in the spectral power of the low theta band, and a decrease in the gamma. These results were replicated by intrahippocampal injections of a GABAB antagonist. Thus, the GABAergic septo-hippocampal pathway seems to carry information involved in the encoding of reward properties, where GABAB receptors seem to play a key role. With regard to the dorsal hippocampus, fEPSPs evoked at the CA3-CA1 synapse seem to reflect the BSR learning process, while hippocampal rhythmic activities are more related to reward properties.

Show MeSH