ABSTRACT

1. Modulatory Influence of Auditory Cortex on the Activity of Medial Geniculate Body Neurons in RatR. Moucha1, J. Poeplar2, D. Suta2, M.P. Kilgard1, J. Syka21 School of Behavioral and Brain Sciences, University of Texas at Dallas, USA2 Institute of Experimental Medicine ASCR, Prague, Czech Republic

2. ABSTRACT Cortico-thalamic feedback projections greatly outnumber the ascending thalamo-cortical input fibers, yet there is little understanding of the functional role of these connections. The purpose of this study was to investigate cortico-thalamic modulation in the rat (Long-Evans strain) auditory system. We examined the effects of electrical activation of the deep layers of the auditory cortex on the responses of neurons located in the medial geniculate body (MGB). Extracellular multiunit recordings were collected in the MGB with 16 channel multielectrodes during simultaneous electrical stimulation of the auditory cortex (short train of monophasic pulses, 12.5-200µA). Neuronal responses were evaluated and compared during acoustic stimulation (AS) with broadband noise, electrical stimulation (ES) and paired acoustic and electrical activation (AS+ES). Broadband noise evoked excitatory sustained activation with an increased onset in the majority of MGB sites. This response was mostly suppressed after AS+ES pairing when the delay between ES and AS was between 10 and 30ms and the suppression declined at longer intervals. In most cases the suppression affected the late part of the response. ES alone evoked short latency excitation within 5ms and a longer lasting suppression of spontaneous activity. In some neurons the suppression of spontaneous activity decreased over repetitions of stimulation. At some MGB sites ES triggered late excitatory responses at approximately 200 ms. The relationship between the location of electrical stimulation and its effect on different parts of the MGB are also being examined. This research was supported by GACR grant 309/04/1074.

3. + IV V VI + + + _ RTN MGB AIM OF THE STUDY To investigate the modulatory effects of cortico-thalamic feedback projections MGB receives extensive feedback from cortical layer VI These projection greatly outnumber the ascending fibers from thalamus to the cortex. Direct cortical feedback projections to MGB are excitatory. An important question to answer is how this feedback participates in the specific processing of sensory information

4. METHODS Recording electrode ES AS |||| |||| // 0 15 30 80 800 time (ms) delay 1-2 Tungsten stimulating electrode in A1 Michigan 16 ch recording electrode in MGB Acoustic stimulus = Broadband Noise 50ms duration (AS) Electrical stimulus = 4 monophasic pulses .33ms width, 500Hz (ES) Stimulation = AS alone, AS+ES, ESalone Current = 12.5, 25, 50, 100A , monopolar Delay = 10, 30, 60, 90, 120, 180, 240ms Peristimulus Recording = 400 ms 1set = 100 repeats of one stimulation per 800ms (0.8 Hz) Tracts between 5-6 mm post to Bregma,  A1, @ 4000-5000 depth

5. D p ES+AS ES V A Time (ms) el. pulse Excit. to AS Excit. to ES |||| ES AS 30ms Excitatory Effect of Cortical ES on Thalamic Responses during ES alone (dotted) and ES+AS (solid) Position of stimulating electrode in A1, and MGB recording sites @ 4000  depths Recordings of thalamus action potentials ES elicits short latency (~3-4ms) excitatory responses in MGB In 60% of the units recorded

6. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 MGB Effect of Electrical Stimulation Total recordings: N = 10 rats, under ketamine anesthesia Sites = 384 multiunit recordings from auditory responsive thalamic sites Tracts = 24 (16 tracts in MGv, 5 tracts in MGd, 3 tracts in VPM) Yield = 3-16 channels on each tract

7. Effect of Cortical BF of Stimulated Site • Suppression in ch 1-12, BF’s < 7 kHz (cortical BF = 7 kHz) • Less/no suppression in ch 13-16, BF’s > 7 kHz • All channels are suppressed by ES alone • Ch/CF: 1/?, 2/?, 3/4, 4/3, 5/4, 6/5, 7/4, 8/5, 9/4, 10/6, 11/7, 12/6, • 13/9, 14/12, 15/14, 16/15

8. Immediate Recovery from Suppression

9. Ch 9 Ch 13

10. Effect of Stimulating Current Intensity AS AS+ES_12.5 A AS+ES_25 A AS+ES_50 A N = 48 sites

11. Late evoked excitation, “rebound” from strong inhibition AS AS+ES_50 A AS+ES_25 A In some units stronger ES currents in addition to increasing suppression also evoked a late excitatory response @ 200 ms from ES onset

12. Effect of Delay between ES and AS : 30, 90, 180 ms 180 ms N = 64 sites 90ms 30ms

13. Responses to AS at increasing delays between AS and ES Mean response of 16 channels from one MGB tract Difference in mean spikes evoked over 70 ms from the response onset Delay –30 ms indicates reversed order between ES and AS (i.e. AS precedes ES by 30ms)

14. Types of MGB responses to AS, in 3 units from the same tract Onset only (37%) On + Off (15%) Onset & sustained (48%) Stability over time: dotted line is response to AS (broadband noise 50ms) after 30 min, shifted

15. Raster plots of Responses from 3 units to 100 reps of AS, and AS+ES PSTH’s of the Responses presented above during AS and AS+ES

16. Effect of Cortical Blockade by Muscimol on MGB Responses Pre Musc AS AS+ES Post 30 min AS AS+ES • No effect of ES during cortical inactivation • (i.e. no suppression of AS response during cortical stimulation under Muscimol) • Late responses are abolished • Response latency is increased Pre Muscimol Post 10 min Post 30 min Post 1hr Post 2 hrs

17. CONCLUSIONS • Electrical activation of A1 suppresses the response of • MGB neurons to subsequent acoustic stimuli delivered • within 30 ms after ES, and facilitates the responses at • delays greater than 90 ms. • The magnitude of suppression increases with the • intensity of stimulating current • (more suppression if more current). • There is no lasting effect of electrical stimulation, • MGB responses recover to baseline immediately after A1 • stimulation stops.