Frequency-Dependent, Cell Type-Divergent Signaling in the Hippocamposeptal Projection

Abstract

Hippocampal oscillations are critical for information processing, and are strongly influenced by inputs from the medial septum. Hippocamposeptal neurons provide direct inhibitory feedback from the hippocampus onto septal cells, and are therefore likely to also play an important role in the circuit; these neurons fire at either low or high frequency, reflecting hippocampal network activity during theta oscillations or ripple events, respectively. Here, we optogenetically target the long-range GABAergic projection from the hippocampus to the medial septum in rats, and thereby simulate hippocampal input onto downstream septal cells in an acute slice preparation. In response to optogenetic activation of hippocamposeptal fibers at theta and ripple frequencies, we elicit postsynaptic GABAergic responses in a subset (24%) of septal cells, most predominantly in fast-spiking cells. In addition, in another subset of septal cells (19%) corresponding primarily to cholinergic cells, we observe a slow hyperpolarization of the resting membrane potential and a decrease in input resistance, particularly in response to prolonged high-frequency (ripple range) stimulation. This slow response is partially sensitive to GIRK channel and D2 dopamine receptor block. Our results suggest that two independent populations of septal cells distinctly encode hippocampal feedback, enabling the septum to monitor ongoing patterns of activity in the hippocampus.

Serotonin increases synaptic activity in olfactory bulb glomeruli

“…In agreement with this, current-clamp recordings of SACs showed a small but significant depolarization in 5HT (2.4 Ϯ 0.3 mV; n ϭ 7, P Ͻ 0.01; not shown). We estimated the reversal potential for the 5HT current to be Ϫ26.2 Ϯ 5.9 mV (Mattis et al 2014, see MATERIALS AND METHODS). Thus it is consistent with a mixed cation conductance and has a greater driving force at more negative resting membrane potentials.…”

“…The reversal potential of the 5HT response in SACs and MCs was estimated using the brief voltage steps to measure input resistance. From measurements of the 5HT-evoked current at Ϫ60 and at Ϫ65 mV, we created a simple, two-step current-voltage curve assuming the simple addition of linear membrane conductances (Mattis et al 2014).…”

Integration of optogenetics with complementary methodologies in systems neuroscience

“…1a). Some commonly used promoter fragments that confer cell type preference and are applicable in lentivirus or adeno-associated virus (AAV) vectors are linked to the following markers 73 : calcium/calmodulin-dependent protein kinase type II subunit-α (CaMKIIα; biased towards excitatory cells in cortical regions 3,4 ), hypocretin 74 , oxytocin 75 , D2 dopamine receptor 41 , glial fibrillary acidic protein (GFAP; for astrocytes), myelin basic protein (MBP; for oligodendrocytes) and somatostatin 76 . This method has illuminated how hypocretin-producing lateral hypothalamic neurons regulate sleep–wake transitions 74 and how nucleus accumbens (NAc) D2 dopamine receptor-expressing cells modulate risk taking 41 .…”

A model of cholinergic suppression of hippocampal ripples through disruption of balanced excitation/inhibition

“…Our previous work has shown that gain modulation in cholinergic MS‐DB neurons is possible with hyperpolarization (Melonakos, White, & Fernandez, ). Further, hippocamposeptal (somatostatin + GABAergic) neurons most effectively evoke hyperpolarization in cholinergic MS‐DB neurons when driven at 50 Hz (Mattis et al, ). Since optogenetic activation of cholinergic MS‐DB neurons blocks ripples in the hippocampus, while increasing theta power and coherence (Vandecasteele et al, ), it would be interesting to see if 50 Hz somatostatin + GABAergic neuron firing could reduce gain in cholinergic neurons, reducing their output and increasing the incidence of ripples.…”