Postsynaptic and Spiking Activity of Pyramidal Cells, the Principal Neurons in the Rat Hippocampal CA1 Region, Does Not Control the Resultant BOLD Response: A Combined Electrophysiologic and fMRI Approach

Abstract

The specific role of postsynaptic activity for the generation of a functional magnetic resonance imaging (fMRI) response was determined by a simultaneous measurement of generated field excitatory postsynaptic potentials (fEPSPs) and blood oxygen level-dependent (BOLD) response in the rat hippocampal CA1 region during electrical stimulation of the contralateral CA3 region. The stimulation electrode was placed either in the left CA3a/b or CA3c, causing the preferentially basal or apical dendrites of the pyramidal cells in the right CA1 to be activated. Consecutive stimulations with low-intensity stimulation trains (i.e., 16 pulses for 8 seconds) resulted in clear postsynaptic responses of CA1 pyramidal cells, but in no significant BOLD responses. In contrast, consecutive high-intensity stimulation trains resulted in stronger postsynaptic responses that came along with minor (during stimulation of the left CA3a/b) or substantial (during stimulation of the left CA3c) spiking activity of the CA1 pyramidal cells, and resulted in the generation of significant BOLD responses in the left and right hippocampus. Correlating the electrophysiologic parameters of CA1 pyramidal cell activity (fEPSP and spiking activity) with the resultant BOLD response revealed no positive correlation. Consequently, postsynaptic activity of pyramidal cells, the most abundant neurons in the CA1, is not directly linked to the measured BOLD response.

Hippocampal CA3 activation alleviates fMRI-BOLD responses in the rat prefrontal cortex induced by electrical VTA stimulation

“…In the first set of experiments, the left CA3-region was stimulated with 10 consecutive stimulation trains followed by a stimulation of the VTA with 5 stimulation trains and finally, the two regions were simultaneously stimulated with 10 consecutive trains (n = 11). As previously observed [ 4 ], repetitive stimulation of the left CA3 region resulted in significant BOLD responses in the left and right hippocampus and the lateral and medial septal nuclei ( Fig 2 ). At this low frequency, no significant changes in BOLD signal intensities were observed in the mPFC/ACC region.…”

“…Similarly, the mPFC receives glutamatergic projections from hippocampal CA1 and subicular pyramidal cells [ 20 , 21 ]. In contrast to high-frequency VTA stimulation, low frequency stimulation of the left CA3 region did not induce significant BOLD responses in the mPFC/ACC, a result that confirms two previous studies [ 4 , 5 ]. Thus, putative variations in neuronal activities in the mPFC/ACC induced by hippocampal afferents were not sufficient to induce detectable hemodynamic responses; this requires pulse frequencies of 10 Hz or higher, which in turn caused the formation of positive BOLD responses in the mPFC [ 5 ].…”

“…To address the question of how reliable BOLD-fMRI detects existing functional connectivities under different conditions, we modified this experimental approach and activated separately and/or concurrently two partially overlapping brain-wide neuronal networks. First, the left hippocampal CA3 region was electrically activated, which has previously be shown to induce significant BOLD responses in the left and right hippocampus and septum [ 4 ] and potentially in the prefrontal cortex [ 5 ] and second, the ventral tegmental area (VTA) was electrically activated, which has previously been shown to cause the formation of significant BOLD responses in the VTA, septum, prefrontal cortex, and parts of the hippocampus [ 6 ]. The VTA is linked with a number of brain regions, such as the nucleus accumbens (NAcc), medial prefrontal cortex (mPFC/ACC), hippocampus, amygdala, and septum [ 7 – 10 ].…”

Psychedelics

“…A primary action of psilocybin may be to cause a generalized desynchrony and loss of oscillatory power in higher-level cortical regions, probably resulting from activation of serotonin 5-HT 2A receptors expressed on deep-later pyramidal neurons. Scherf and Angenstein (2015) simultaneously measured generated field EPSPs and BOLD response in the CA1 region of the rat hippocampus during electrical stimulation of the contralateral CA3 region. Consecutive stimulations with low-intensity stimulation trains resulted in clear postsynaptic responses of CA1 pyramidal cells, but no significant BOLD response.…”

Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

“…Taking advantage of the well-defined synaptic circuitry of the hippocampal formation, Angenstein et al ( 2007, 2009 ) have utilized direct current stimulation and neural recordings across a series of studies to determine the relationship between local field activity and the BOLD signal, particularly in relation to its evoked spatial and temporal properties in hippocampus ( Tiede et al, 2012 ; Angenstein, 2014 ; Scherf and Angenstein, 2015 ). Electrical stimulation of afferents and recording in specific hippocampal regions allowed this group to control input activity to the dorsal CA1/dentate region, where BOLD signals were measured.…”